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ABSTRACT: Previous studies have demonstrated that acute lung injury (ALI) is associated with significant mortality and so far no effective pharmacotherapy is shown to reverse the natural progression. This study aims to investigate whether the transplantation of bone marrow derived mesenchymal stem cells (MSCs) might restore damaged pulmonary function and tissue structure in ALI. By using a sublethal chest impact injury plus endotoxemia model, MSCs were intravenously transplanted into the injured rats 2h after trauma. The blood samples were obtained for determination of blood gas. Bronchoalveolar lavage fluid (BALF) was collected for analysis of inflammatory cell count and cytokine (TNF-α, IL-1β, IL-6 and IL-10) levels. The left lower lobes of the lungs, nearby the impact zone, were collected for SRY gene analysis and histological examination and scoring. After engraftment of MSCs, the number of inflammatory cells in BALF was decreased. Meanwhile, the secretions of pro-inflammatory TNF-α and IL-6 were alleviated, while the secretion of anti-inflammatory IL-10 was elevated. Engraftment of MSCs improved the pulmonary gas exchanges, alleviated the lung injury, and reduced the rats' mortality. These results suggested that the MSCs based measures might be a promising strategy in trauma and endotoxemia induced ALI treatment.
International immunopharmacology 12/2012; · 2.21 Impact Factor
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ABSTRACT: Objective: To explore the changes of Treg-Th17 balance influenced by corticosterone, major effect hormone of hypothalamic-pituitary-adrenal (HPA) axis under running stress. Methods: A total of 25 corticotropin-releasing hormone (CRH) wildtype (CRH+/+) and knockout (CRH-/-) mice were adopt and divided into 4 groups as follows: CRH+/+ ctrl, CRH+/+ stress, CRH-/- ctrl and CRH-/- stress. All mice in stress groups were under 2 h running. After 1 h, blood plasma in all groups was collected and the expression of corticosterone and IL-17A was detected by ELISA. Meanwhile, unicell suspensions of peripheral lymph node and spleen in each group were prepared too and stained by PE-CD4 and FITC-CD25, then the changes of Treg (CD4+CD25+) in different groups were checked by flow cytometry; all data were statistically analyzed by the software of WinMDI 2.9, SPSS 11.5, Origin 7.5 and Matlab 2-D and 3-D plot function. Results: The levels of corticosterone were significantly higher in stress groups than that in corresponding control groups (P less than 0.05), especially in CRH+/+ stress group (P less than 0.01). However, the changes of Tregs were not obvious between stress groups and control groups with respective genotypes (P less than 0.05). Compared with that in CRH+/+ control group, the ratio of Treg and the expression of IL-17A in CRH-/- stress group were significantly higher than those in control group (P less than 0.05). Combined with the expression levels of corticosterone, Treg and Th17, our study suggests that endogenous glucocorticoid with basal level may cause the changes in Treg-Th17 balance. Moreover, as the corticosterone level increases, the expression of Treg and Th17 appears to manifest antagonistic fluctuant status with a rising tendency in general. Conclusion: Endogenous glucocorticoid under early stage of stress may increase the function of T lymphocyte immunity to some extent.
Chinese Journal of Traumatology (English Edition) 12/2012; 15(6):323-8.
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Li Li, Wei Gu,
Juan Du,
Brian Reid,
Xianjian Deng,
Zhidai Liu,
Zhaowen Zong,
Haiyan Wang,
Bo Yao,
Ce Yang,
Jun Yan,
Ling Zeng,
Laura Chalmers,
Min Zhao,
Jianxin Jiang
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ABSTRACT: Migration of epidermal stem cells (EpSCs) into wounds may play an important role in wound healing. Endogenous electric fields (EFs) arise naturally at wounds. Consistent with previous reports, we measured outward electric currents at rat skin wounds using vibrating probes. Topical use of prostaglandin E2 significantly promoted wound healing. However, it is not known whether EpSCs respond to EFs. We first isolated and characterized EpSCs from rat skin. We then demonstrated that EpSCs isolated from the epidermis migrated directionally toward the cathode in EFs of 50-400 mV/mm. The directedness values increased in a dose- and time-dependent fashion. The migration speed of EpSCs was significantly increased in EFs. EFs induced asymmetric polymerization of intracellular F-actin and activation of the extracellular signal-regulated kinase 1/2 and phosphatidylinositol-3-kinase (PI3K)/protein kinase B pathways. Inhibition of epidermal growth factor receptor, extracellular signal-regulated kinase 1/2, or PI3K significantly inhibited the cathodal distribution of F-actin and the electrotactic response of EpSCs. These data for the first time show that EpSCs possess obvious electrotaxis, in which the epidermal growth factor receptor-mitogen activated protein kinase-PI3K pathways are involved. These data thus suggest a novel aspect of electric signaling in wound healing-to stimulate and guide migration of EpSCs and to regulate wound healing.
Wound Repair and Regeneration 10/2012; · 2.91 Impact Factor
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Ling Zeng,
An-Qiang Zhang, Wei Gu,
Jian Zhou,
Lian-Yang Zhang,
Ding-Yuan Du,
Mao Zhang,
Hai-Yan Wang,
Jun Yan,
Ce Yang,
Jian-Xin Jiang
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ABSTRACT: INTRODUCTION: The receptor for advanced glycation end products (RAGE) has been considered as one of the major pattern recognition receptors and plays an important role in the development of sepsis and multiple organ dysfunction in critical illnesses. Although genetic variants of the RAGE gene have been shown to be well associated with susceptibility to some inflammatory diseases, little is known about their clinical relevance in the development of sepsis in critical ill patients. METHODS: Four genetic variants were selected from the entire RAGE gene and genotyped using pyrosequencing and polymerase chain reaction-length polymorphism methods. Association studies were performed in two independent Chinese Han populations. RESULTS: Among the four genetic variants, only the rs1800625 polymorphism was significantly associated with sepsis morbidity rate and multiple organ dysfunction (MOD) scores in patients with major trauma both in Chongqing (n = 496) and Zhejiang (n = 232) districts, respectively. Results from ex vivo responsiveness of peripheral blood leukocytes indicated that the rs1800625 polymorphism was well associated with decreased production of TNFα. In addition, the rs1800625 polymorphism could significantly inhibit the promoter activities of the RAGE gene. CONCLUSIONS: The rs1800625 polymorphism is a functional variant, which might be used as a relevant risk estimate for the development of sepsis and multiple organ dysfunction syndrome in patients with major trauma.
Critical care (London, England) 07/2012; 16(4):R131. · 4.61 Impact Factor
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ABSTRACT: Myeloid differentiation 2 (MD-2) plays a critical role in orchestrating the innate immune response and the development of sepsis and subsequent organ dysfunction after trauma. The objectives of this prospective study were to identify haplotype tag single-nucleotide polymorphisms (htSNPs) within the entire MD-2 gene and to investigate their clinical relevance in patients with major trauma. A total of 726 patients with major trauma were prospectively recruited and composed of two different geographic populations (Chongqing in southwestern China and Zhejiang in eastern China). The htSNPs of the MD-2 gene were determined using HapMap database and linkage disequilibrium analysis. The htSNPs were genotyped using pyrosequencing method. The whole peripheral blood samples obtained immediately after admission were stimulated with bacterial lipopolysaccharide and then determined for production of tumor necrosis factor α. Sepsis morbidity rate and multiple organ dysfunction (MOD) scores were accessed. Three SNPs (rs7843858, rs11465996, and rs2114169) were identified as htSNPs for the MD-2 gene. All of them were shown to be high-frequent SNPs in this study cohort. However, only the rs11465996 polymorphism was shown to be significantly associated with higher sepsis morbidity rate and MOD scores in patients with major trauma in both Chongqing and Zhejiang districts. In addition, the rs11465996 polymorphism was significantly associated with tumor necrosis factor α production by peripheral blood leukocytes in response to bacterial lipoprotein stimulation. Among the three htSNPs of the entire MD-2 gene, only the rs11465996 might be used as relevant risk estimate for the development of sepsis and MOD syndrome in patients with major trauma.
Shock (Augusta, Ga.) 01/2012; 37(4):366-72. · 2.87 Impact Factor
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ABSTRACT: To determine the hypothesis that genetic variations of the lipopolysaccharide-binding protein (LBP) gene influence risk for the development of sepsis and multiple organ dysfunction (MOD) in patients with major trauma.
Lipopolysaccharide-binding protein plays a central role in innate immune response as the first line of defense and directing the microbial-induced activation of the inflammatory host response. Although a total of 112 single nucleotide polymorphisms (SNPs) have been identified so far within the entire LBP gene, only a few SNPs have been studied.
Nine haplotype tagging SNPs (htSNPs) were selected from 51 SNPs with a minor allele frequency of ≥5% using the HapMap database for the Chinese Han population. Two independent cohorts of major trauma patients were recruited. The 9 htSNPs were genotyped using pyrosequencing method and analyzed in relation to the risk of development of sepsis and MOD, LBP production, and lipopolysaccharide (LPS)-induced activation of peripheral blood leukocytes. Moreover, the functionality of the rs2232618 polymorphism was assessed by the observation of its effects on the binding and activation of LPS and the LBP-CD14 interaction.
Among the 9 htSNPs, only the rs2232618 was significantly associated with higher susceptibility to sepsis and MOD in the 2 independent cohorts of major trauma patients recruited from southwest and eastern China. This SNP was also significantly associated with LPS-induced activation of peripheral blood leukocytes. In addition, the rs2232618 polymorphism could enhance LBP protein activities, showing significant increases in LPS binding to macrophages, LPS-induced cellular activation, and LBP-CD14 interaction at the presence of the variant LBP protein.
The rs2232618 polymorphism is a functional SNP and confers host susceptibility to sepsis and multiple organ dysfunction in patients with major trauma.
Annals of surgery 12/2011; 255(1):147-57. · 7.90 Impact Factor
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An-Qiang Zhang,
Ling Zeng, Wei Gu,
Lian-Yang Zhang,
Jian Zhou,
Dong-po Jiang,
Ding-Yuan Du,
Ping Hu,
Ce Yang,
Jun Yan,
Hai-Yan Wang,
Jian-Xin Jiang
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ABSTRACT: The nucleotide-binding oligomerization domain-like receptor (NLR) family has been recognized as comprising intracellular pattern recognition receptors in which NLRP3 (NLR family, pyrin domain containing 3) plays an important role in the initiation of host immune inflammatory responses. The genetic variants have been recognized to be critical determinants of interindividual differences in both inflammatory responses and clinical outcomes in critical illness. However, little is known about the clinical relevance of NLRP3 gene polymorphisms in critical illness.
A total of 718 patients with major blunt trauma were included in this study. Six tag SNPs (tSNPs) were selected from the entire NLRP3 gene through construction of haplotype bins, and they were genotyped using a pyrosequencing method. They were analyzed in relation to sepsis morbidity rate, multiple organ dysfunction (MOD) scores and IL-1β production. Moreover, the functionality of the rs2027432 polymorphism was assessed by the observation of its effect on transcriptional activities.
Among the six tSNPs genotyped in this study, two of them (rs2027432 and rs12048215) were significantly associated with sepsis morbidity rate and MOD scores. A significant association was also observed between these two polymorphisms and IL-1β production by peripheral leukocytes in response to ex vivo lipopolysaccharide stimulation. However, no combined effects were found between these two polymorphisms. In addition, the rs2027432 polymorphism could significantly enhance the promoter activities of the NLRP3 gene.
rs2027432 and rs12048215 polymorphisms might be used as relevant risk estimates for the development of sepsis and MOD syndrome in patients with major trauma, in which rs2027432 might be a functional SNP.
Critical care (London, England) 11/2011; 15(6):R280. · 4.61 Impact Factor
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Ling Zeng,
An-Qiang Zhang, Wei Gu,
Ke-Hong Chen,
Dong-Po Jiang,
Lian-Yang Zhang,
Ding-Yuan Du,
Ping Hu,
Su-Na Huang,
Hai-Yan Wang,
Jian-Xin Jiang
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ABSTRACT: High-mobility group box protein 1 (HMGB1) is a pivotal late mediator involved in the development of sepsis and multiple organ dysfunction syndrome (MODS) in critically ill patients. While several single nucleotide polymorphisms (SNPs) have been demonstrated to be critical determinants for outcome of critically ill patients, little is known about the clinical relevance of SNPs of the HMGB1 gene up to date.
A total of 3 tag SNPs of the HMGB1 gene were selected using HapMap database and linkage disequilibrium analysis. The tag SNPs were genotyped using a pyrosequencing methodology in 556 unrelated patients with major trauma. Peripheral whole blood samples obtained immediately after admission were determined for HMGB1 production in response to ex vivo lipopolysaccharide (LPS) stimulation.
The rs2249825 SNP and the haplotype TCG were significantly associated with LPS-induced HMGB1 production by peripheral blood leukocytes. There were also significant differences in sepsis morbidity rate and MOD scores among patients with different genotypes of the rs2249825. In addition, the patients with the wild-type haplotype TCG had a lesser sepsis morbidity rate and MOD scores than those without the TCG haplotype.
A total of 3 SNPs might act as tag SNPs for the entire HMGB1 gene. The rs2249825 and the haplotype TCG might be used as relevant risk estimate for the development of sepsis and MODS in patients with major trauma.
Surgery 11/2011; 151(3):427-36. · 3.10 Impact Factor
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ABSTRACT: Tumor necrosis factor (TNF) is a proinflammatory cytokine that plays a major role in the sepsis and multiple organ dysfunction secondary to major trauma. The purpose of this article was to research the clinical relevance of the TNF gene polymorphism in patients with major trauma.
Three hundred six patients with major trauma were prospectively recruited. The TNF gene polymorphisms were genotyped using restriction fragment length polymorphism analysis. Plasma TNF-α levels were determined with enzyme-linked immunosorbent assay. Sepsis morbidity rate and multiple organ dysfunction scores were accessed.
The TNF-α/-308 polymorphism was shown to be well associated with increased capacity of peripheral leukocytes to produce TNF-α in response to ex vivo lipopolysaccharide stimulation in trauma patients at admission. Results from association study indicated that trauma patients carrying the TNF-α/-308/A allele were more likely complicated with sepsis.
The TNF-α/-308 polymorphism might be used as a biomarker for the assessment of outcome of trauma patients, but the TNF-β/252 gene polymorphism might not influence the development of complications in patients with major trauma.
The Journal of trauma 04/2011; 70(4):954-8. · 2.48 Impact Factor
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ABSTRACT: Interleukin (IL)-4 is a pleiotropic cytokine, severed as an important component of the adaptive immune system, and implicated in the pathophysiology of sepsis. Data from other studies show that the -589T/C polymorphism in IL-4 promoter may alter IL-4 expression and susceptibility of inflammatory or autoimmune diseases. Whether this genetic variation is associated with sepsis susceptibility is unknown. The aim of this study was to search for the association of IL-4 -589T/C with the susceptibility to sepsis.
The polymorphism was genotyped among 308 severe trauma patients using restriction fragment length polymorphism polymerase chain reaction. The IL-4 and interferon-γ levels in the supernatants were determined with enzyme-linked immunosorbent assay.
The IL-4/-589C allele was shown to be significantly associated with higher plasma IL-4 and lower interferon-γ production after lipopolysaccharide stimulation, indicating its effect on regulating T helper T(H)1/T(H)2 balance. Moreover, homozygosity and heterozygosity for the -589C were associated with an increased susceptibility of sepsis (p = 0.009; OR, 1.69; 95% confidence interval, 1.14-2.51). There was no relationship between the IL-4 -589T/C and multiple organ dysfunction scores in severe trauma patients.
These results suggest that the IL-4 -589T/C polymorphism might affect T(H)1/T(H)2 balance and predispose trauma patients to susceptibility sepsis.
The Journal of trauma 03/2011; 71(6):1583-7. · 2.48 Impact Factor
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Ke-Hong Chen, Wei Gu,
Ling Zeng,
Dong-Po Jiang,
Lian-Yang Zhang,
Jian Zhou,
Ding-Yuan Du,
Ping Hu,
Qing Liu,
Su-Na Huang,
Jian-Xin Jiang
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ABSTRACT: Toll-like receptor 2 (TLR2) signaling plays a critical role in orchestrating the innate immune response and the development of sepsis and subsequent organ dysfunction after trauma. The objectives of this prospective study were to identify haplotype tag single-nucleotide polymorphisms (htSNPs) within the entire TLR2 gene and to investigate their clinical relevance in patients with major trauma. A total of 410 patients with major trauma were prospectively recruited. The htSNPs of the TLR2 gene was determined using HapMap database and linkage disequilibrium analysis. The htSNPs were genotyped using polymerase chain reaction-restriction fragment length polymorphism method. The whole peripheral blood samples obtained immediately after admission were stimulated with bacterial lipoprotein and then determined for production of tumor necrosis factor-α, interleukin 8, and interleukin 10. Sepsis morbidity rate and multiple organ dysfunction (MOD) scores were accessed. Three SNPs (rs1898830, rs3804099, and rs7656411) were identified as htSNPs for the TLR2 gene. All of them were shown to be high-frequency SNPs in this study cohort. Two of them (rs1898830 and rs3804099) and the haplotype ATT were significantly associated with cytokine production by peripheral blood leukocytes in response to bacterial lipoprotein stimulation. Only rs3804099, however, was significantly associated with higher sepsis morbidity rate and MOD scores in patients with major trauma. In addition, the patients with the haplotype ATT had lower sepsis morbidity rate than those without the haplotype ATT. Therefore, three SNPs might act as htSNPs for the entire TLR2 gene in the Chinese population. The rs3804099 and the haplotype ATT might be used as relevant risk estimates for the development of sepsis and MOD in patients with major trauma.
Shock (Augusta, Ga.) 01/2011; 35(1):35-41. · 2.87 Impact Factor
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Wei Gu,
Ling Zeng,
Jian Zhou,
Dong-po Jiang,
Lianyang Zhang,
Ding-yuan Du,
Ping Hu,
Kehong Chen,
Qin Liu,
Zheng-guo Wang,
Jian-xin Jiang
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ABSTRACT: To determine the clinical relevance of 13 reported common single-nucleotide polymorphisms (SNPs) of cytokine genes in patients with major trauma.
Thirteen SNPs in nine key cytokine genes were selected for association study in 308 patients with major trauma on the basis of previous functional or association data. An allele-specific oligonucleotide array was developed and used to genotype 308 patients with major trauma. The clinical relevance of the 13 SNPs was assessed by observation of cytokine production and outcome of trauma patients.
Results from the allele-specific oligonucleotide array indicated that 8 [interleukin-1beta (IL-1beta)/-1470, IL-1beta/-511, IL-1beta/-31, IL-4/-589, IL-6/-572, IL-8/-251, IL-10/-819, and tumor necrosis factor alpha (TNFalpha)/-308] out of the 13 SNPs were associated with respective ex vivo cytokine production by peripheral leukocytes in response to lipopolysaccharide (LPS) stimulation at admission, or risk of development of sepsis or organ dysfunction in major trauma patients. Patients with more than four risk alleles of the eight SNPs had more than 50% sepsis morbidity and more severe organ dysfunction.
Polymorphisms of IL-1beta/-1470, IL-1beta/-511, IL-1beta/-31, IL-4/-589, IL-6/-572, IL-8/-251, IL-10/-819, and TNFalpha/-308 are susceptibility loci for the development of sepsis and organ dysfunction in major trauma patients.
European Journal of Intensive Care Medicine 03/2010; 36(7):1261-5. · 5.17 Impact Factor
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Kehong Chen,
Yong-tang Wang, Wei Gu,
Ling Zeng,
Dong-po Jiang,
Ding-yuan Du,
Ping Hu,
Zhao-xia Duan,
Qing Liu,
S N Huang,
Jian-xin Jiang
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ABSTRACT: Toll-like receptor 4 is an important signaling receptor for lipopolysaccharide in mammals, and the variation of the promoter may affect the activity of toll-like receptor 4 expression. Although 12 single nucleotide polymorphisms have been identified in the toll-like receptor 4 promoter, little is known about the functional significance of these single nucleotide polymorphisms.
Genetic functional and association studies.
National Key Laboratory of Trauma and Departments of Traumatic Surgery in two teaching hospitals.
Three hundred seventy-nine healthy volunteers and 303 patients with major trauma.
None.
Five single nucleotide polymorphisms identified in the toll-like receptor 4 promoter in the Chinese Han population were selected. Three of them revealed a close relationship with transcription factor binding sites. Among the three single nucleotide polymorphisms, only the T-2242C polymorphism significantly increased transcriptional activities of the toll-like receptor 4 promoter, as shown by reporter gene assay. Results from flow cytometry and ex vivo responsiveness of peripheral blood leukocytes indicated that the T-2242C polymorphism was well-associated with increased expression of toll-like receptor 4 protein and production of tumor necrosis factor-alpha. The clinical relevance of these single nucleotide polymorphisms was then investigated in 303 patients with major trauma. The peripheral blood leukocytes of trauma patients with the variant C allele revealed greater capacity to produce tumor necrosis factor-alpha and interleukin-6 on the admission day. Furthermore, the toll-like receptor 4/2242 polymorphism was significantly associated with higher sepsis morbidity rates and multiple organ dysfunction scores in patients with major trauma.
The toll-like receptor 4/2242 polymorphism is a functional variant and might be used as a relevant risk estimate for organ dysfunction and sepsis in trauma patients.
Critical care medicine 03/2010; 38(5):1292-9. · 6.37 Impact Factor
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ABSTRACT: Major trauma is the leading cause of death in young adults. Despite advances in prehospital system and treatment in hospital, mortality rates have not improved significantly over the past decades. Victims of severe injuries who survive the initial hours have great risk for additional life-threatening complicaitons, including uncontrollable infection (sepsis) and multiple organ dysfunction syndrome (MODS). Single nucleotide polymorphisms (SNPs) have been shown to affect susceptibility to the course of numerous diseases. Accumulating evidence suggests that genetic backgrounds also play important roles in posttraumatic complications. Genetic polymorphisms may become powerful biomarkers for diagnosis and prognosis of trauma-induced complications. Recent advances in studies on associations between genetic polymorphisms and sepsis or MODS have led to better understanding of posttraumatic complications. Here we summarise recent findings on genetic variations in molecules of the innate immune system and other systems as well as their connection with susceptibility to posttraumatic complications.
Comparative and Functional Genomics 01/2010; 2010:814086. · 1.28 Impact Factor
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ABSTRACT: To investigate the clinical relevance of the TLR4 11367 polymorphism in patients with major trauma.
Genetic functional and association study.
Daping Hospital and Chongqing Emergency Medical Center, Chongqing, China.
A total of 132 patients with major trauma were prospectively recruited.
The TLR4 11367 polymorphism was genotyped using single-tube, bidirectional, allele-specific amplification method. Whole peripheral blood samples obtained within 24 hours after admission were stimulated with lipopolysaccharide and then tested for production of tumor necrosis factor alpha and interleukin 6. Sepsis morbidity rate and multiple organ dysfunction scores were assessed.
The 11367 polymorphism was shown to be strongly associated with less capacity of peripheral leukocytes to produce tumor necrosis factor alpha and interleukin 6 in response to ex vivo lipopolysaccharide stimulation in patients with trauma at admission. Results from association study indicated that patients with trauma who carry the 11367C allele were less likely to have sepsis and multiple organ dysfunction.
Combined with our previous in vitro functional study, the results suggest that the TLR4 11367 polymorphism might be a good predictor of who is more likely to develop complications such as sepsis or multiple organ dysfunction syndrome, depending on genotype.
Archives of surgery (Chicago, Ill.: 1960) 12/2009; 144(12):1144-8. · 4.32 Impact Factor
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Critical care (London, England) 11/2009; · 4.61 Impact Factor
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ABSTRACT: Recent reports have indicated that IL-1[beta] is excessively released into the circulation during sepsis, and the expression level is closely correlated with the clinical course. Polymorphisms in the promoter region of IL-1B have been shown to affect LPS-induced IL-1[beta] transcription in vitro and IL-1[beta] plasma levels in healthy adults and to confer susceptibility to inflammatory diseases. However, it is not clear whether they confer susceptibility to sepsis after major trauma. The aim of this study was to search for association of polymorphisms (-1470G/C, -511T/C, and -31C/T) in the IL-1B gene promoter with the susceptibility to sepsis in a cohort of 238 major trauma patients. Genotyping of each patient for the three single-nucleotide polymorphisms was performed by restriction fragment length polymorphism-polymerase chain reaction method. Multivariate logistic regression analysis showed that the -1470 and -31 polymorphisms were associated with IL-1[beta] production by peripheral leukocytes in response to ex vivo LPS stimulation in an allele dose-dependent manner. Moreover, trauma patients carrying the -1470G or -31T alleles were more likely to develop sepsis compared with those with the -1470C or -31C allele (P = 0.014 and P = 0.038, respectively). Of the eight possible haplotypes composed of the three loci, the GCT and CTC haplotypes were associated with significantly higher and lower IL-1[beta] secretion (P = 0.005 and P = 0.035, respectively). Moreover, the GCT haplotype imparted higher risk of sepsis after severe injury (P = 0.04; odds ratio, 1.131; 95% confidence interval, 1.013-1.678). GCT homozygote patients also showed higher multiple organ dysfunction scores than CTC homozygote patients (P = 0.048). These data suggest that the IL-1[beta] promoter polymorphisms -1470G/C, -511T/C, and -31C/T may be functional both in vitro and in vivo. It may be possible to use these polymorphisms as relevant risk estimates for sepsis in trauma patients.
Shock (Augusta, Ga.) 11/2009; 33(6):576-82. · 2.87 Impact Factor
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ABSTRACT: To investigate in a Chinese population the occurrence of polymorphisms Bcl I, N363S and ER22/23EK in the glucocorticoid receptor and their association with outcome of trauma.
In all, 266 healthy volunteers and 95 victims of major trauma were recruited. The presence of glucocorticoid receptor polymorphisms (ER22/23EK, N363S and Bcl I) was sought by restriction fragment length polymorphism analysis. The injured group were monitored as to respiratory, renal, hepatic, cardiovascular, haematological and central nervous functions. The association was determined between polymorphisms and the development of multiple organ dysfunction syndrome and sepsis after trauma.
Only the Bcl I polymorphism was identified. The frequency of its G allele was 23.5% among volunteers and 26.3% among casualties. There were no significant differences in MOD score or sepsis rate between participants classified according to genotype.
Only the Bcl I polymorphism of the glucocorticoid receptor gene is common in the Chinese Han population; it may not influence the development of complications following major trauma.
Injury 03/2009; 40(5):479-83. · 1.98 Impact Factor
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Wei Gu,
Hong Dong,
Dong-Po Jiang,
Jian Zhou,
Ding-Yuan Du,
Jin-Mou Gao,
Yuan-Zhang Yao,
Lian-Yang Zhang,
Ai-Qing Wen,
Qing Liu,
Zheng-Guo Wang,
Jian-Xin Jiang
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ABSTRACT: Several polymorphisms in the CD14 promoter have been reported to be associated with various inflammatory diseases. However, conflicting results have been shown in association studies in different populations. This study aimed to investigate the possible functional significance of both the G-1145A and T-159C polymorphisms in the CD14 promoter and their association with organ dysfunction and sepsis in adult trauma patients.
Genetic, functional, and association studies.
National Key Laboratory of Trauma and Departments of Traumatic Surgery in two teaching hospitals.
Three hundred twenty-five healthy volunteers and 105 patients with major trauma.
None.
Among the five single nucleotide polymorphisms identified within CD14 promoter in a Chinese Han population, two single nucleotide polymorphisms (G-1145A and T-159C) were selected according to bioinformatics analysis. Promoter activity of polymorphisms was determined using the reporter gene assay. Plasma sCD14 and tumor necrosis factor-alpha levels were measured by enzyme-linked immunosorbent assay. Both single nucleotide polymorphisms significantly reduced transcriptional activity of the promoter, and were significantly associated with a decrease of inducible sCD14 and tumor necrosis factor-alpha production in an allele-dose effect. Moreover, trauma patients carrying the -1145 A or -159 C allele appeared to have a decreased risk of multiple organ dysfunction and sepsis. In addition, both polymorphisms had a marked synergistic effect.
The CD14/-1145 and -159 polymorphisms are functional variants, which may function in a synergistic fashion, and could be used as biological risk predictors of multiorgan dysfunction and sepsis in trauma patients.
Critical care medicine 08/2008; 36(8):2274-80. · 6.37 Impact Factor
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ABSTRACT: Interleukin-6 (IL-6) is a pivotal cytokine in both innate and adaptive immunity. Several polymorphisms in the IL-6 promoter have been reported in Western populations. However, little is known about their occurrence in the Chinese population. The functionality of IL-6 promoter polymorphisms remains controversial.
Genetic, functional, and association studies.
National key laboratory of trauma and departments of traumatic surgery in two teaching hospitals.
A total of 348 healthy blood donors and 105 patients with major trauma.
None.
Identification of polymorphisms in the IL-6 promoter was performed using sequencing and restriction fragment length polymorphism methods. Their functionality was assessed by observation of transcription activity, IL-6 production, and their clinical relevance in 105 patients with major trauma. Only one variant (C-572G) was identified in IL-6 promoter in Chinese Han population. This polymorphism was associated with IL-6 production by peripheral leukocytes in response to ex vivo lipopolysaccharide stimulation in an allele-dose-dependent effect. The C-->G variation at position -572 could reduce transcriptional activity of the IL-6 promoter as shown in both U-937 and K562 cell lines. Moreover, the -572 polymorphism was associated with lower risk of sepsis in major trauma patients.
The -572 polymorphism, a unique variation in the IL-6 promoter in the Chinese Han population, may be used as a relevant risk estimate for sepsis in trauma patients.
Critical care medicine 05/2008; 36(5):1437-43. · 6.37 Impact Factor
