ABSTRACT: To investigate the roles of Th17 lymphocytes and its inflammatory cytokines in airway inflammation exacerbation of murine asthmatic model.
Twenty mice were randomized into control group and asthma group. For the murine asthma model, the mice were sensitized and challenged with ovalbumin (OVA). The control mice were given normal saline alone under the same conditions as the asthma group. We observed the changes in cellular proportions in the bronchoalveolar lavage fluid (BALF) under a light microscope and the histological changes in lung tissue by HE staining. The levels of IL-4, IFN-γ and IL-17 were detected by ELISA. Th1, Th2 and Th17 cells in the peripheral blood were detected by flow cytometry. We did a correlation analysis between Th1, Th2 and Th17 cells in the peripheral blood and neutrophils in BALF.
The total cell number and the percentages of neutrophils, eosinophils and lymphocytes in BALF of the asthmatic mice were significantly higher than those in the control mice (P<0.05). The neutrophils and eosinophils infiltration in pulmonary tissue was also dramatically detected in asthmatic mice. The levels of IL-4 and IL-17 were significantly higher than those in the control mice (P<0.05), while the level of IFN-γ was much lower than in the control mice (P<0.05). Besides, the percentages of Th2 and Th17 cells in peripheral blood were significantly higher in the asthmatic mice than in the control mice (P<0.05). The expression of Th17 was positively correlated with the levels of neutrophils in BALF(r(Th17);=0.394, P<0.05), and the expression of Th1 was negatively correlated with the level of neutrophils in BALF (r(Th1);=-0.446, P<0.05).
Th17 cells could induce the recruitment of inflammatory cytokines and neutrophils into airways, which might aggravate the asthmatic inflammation and be related with asthma exacerbation.
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 11/2012; 28(11):1126-8.
ABSTRACT: ABSTRACT Background: Asthma is a chronic inflammatory disease of the airway that is mediated by T-helper 2(TH2) cells. Thymic stromal lymphopoietin (TSLP) can aggravate asthmatic lung inflammation by activating dendritic cells (DCs) to promote TH2 differentiation. TSLP promoter polymorphisms are associated with susceptibility to bronchial asthma in Japanese population. We sought to determine whether single nucleotide polymorphisms (SNPs) in TSLP gene are associated with asthma in Chinese Han population. Objective: To analyze the polymorphism of the two SNPs Rs2289276 and Rs2289278 in TSLP gene and to evaluate the association between the two SNPs and asthma susceptibility in Chinese Han population by using case-control study. Methods: five hundred and thirty one asthmatic patients and 540 age-sex matched normal controls were collected and DNA were extracted from peripheral blood, then the genotypes of SNPs Rs2289276 and Rs2289278 in TSLP gene were detected with polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP), genotype and allele frequencies were calculated and analyzed with Chi-square test. Results: Frequencies of CC/CT/TT genotypes at Rs2289276 site were 0.4706/0.4392/0.0902 in the asthmatic patients and 0.5604/0.3800/0.0595 in the healthy controls. Frequencies of CC/CG/GG genotypes at Rs2289278 site were 0.6502/0.2966/0.0532 in the asthmatic patients and 0.5795/0.3428/0.0777 in the healthy controls. The genotype and allele frequencies of the two SNPs in asthma patients were significantly different from those in the healthy controls. Rs2289278 C allele was correlated with decreased FEV(1): FVC (P ≤ .05). Conclusions: TSLP variants are significantly associated with bronchial asthma. TSLP might be a new therapeutic target molecule for asthma.
Experimental Lung Research 08/2012; 38(8):375-82. · 1.22 Impact Factor
ABSTRACT: To explore the role of interleukin-25(IL-25) in the pathogenesis of eosinophilic asthma (EA) and non-eosinophilic asthma (NEA) through detecting its expression in serum, induced sputum and bronchial epithelial mucosa of asthmatic patients.
Serum and induced sputum were collected from 55 untreated asthmatic patients and 27 healthy control subjects. The asthmatic patients were divided into EA and NEA groups according to sputum eosinophils(EOS) percentage (3% as a dividing point). The level of IL-25 in serum and induced spntum was determined by ELISA; the expression of IL-25 in bronchial epithelium was quantified by immunohistochemistry in biopsied specimens from 10 cases of EA, 10 NEA and 10 controls. Basement membrane thickness as an important index of airway remodeling was detected by HE staining.
Compared with healthy control subjects, the lung function was impaired in patients with EA and NEA. ELISA results showed that the levels of IL-25 in the serum and induced sputum of asthmatic patients were significantly higher than those in healthy subjects (P<0.05). But there were no statistic differences between EA and NEA patients (P>0.05). The immunohistochemical results indicated that the expression of IL-25 was higher in asthmatic bronchial epithelium than in control ones. HE staining showed that the basement membrane thickness increased in EA and NEA patients(P<0.05). Correlation analysis showed that the levels of IL-25 in serum and induced sputum were positively correlated with the average thickness of basement membrane in asthmatic patients.
IL-25 secreted from epithelial cells has the potential to promote airway remodeling in asthma. EOS has nothing to do with the thickness of basement membrane, and it may not be necessary for airway remodeling in asthma.
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 06/2012; 28(6):633-6.