[show abstract][hide abstract] ABSTRACT: This letter reports the influence of branches and bromine substitution of the photosensitizers on one- and two-photon absorption generation of singlet oxygen. Near-infrared femtosecond Ti:squassier laser was utilized to determine two-photon properties of the photosensitizers tuning wavelength from 700 to 880 nm at intervals of 20 nm. One- and two-photon optical and photophysical properties of the photosensitizers show significant dependence on the branches and substituted bromine atoms.
Chinese Science Bulletin 08/2013; 57(30). · 1.32 Impact Factor
[show abstract][hide abstract] ABSTRACT: To investigate the relationship between elevated serum uric acid level and presence of diabetic foot ulcer in Chinese patients with type 2 diabetes.
This was a retrospective study of 829 outpatients with type 2 diabetes (478 maleand 351 female patients) who visited a diabetic clinic, Nanfang Hospital of Southern Medical University, from January 2007 to December 2009. Medical documentations, including clinical history, anthropometric measurements, and laboratory data, were collected. Potential confoundingvariables with P<0.10 were adjusted for in multivariate logistic regression analysis.
In univariate analyses, there was a significant difference in serum uric acid among female patients with and without diabetic foot ulcer (370.1±128.1 vs. 313.1±106.7 μmol/l; P<0.05), but not among male patients (316.5±99.5 vs. 348.3±111.2 μmol/l; P=0.643). The respective prevalences of diabetic foot ulcer among quintiles of uric acid levels were 5.3%, 3.9%, 7.7%, 5.5%, and 16.7% (P-trend=0.018). With uric acid level as a continuous variable, the multivariate-adjusted odds ratio (95% confidence interval) for diabetic foot ulcer in female patients was 1.004 (1.001-1.008) (P<0.05) .
Elevated uric acid level is a significant and independent risk factor for diabetic foot ulcer in female Chinese patients with type 2 diabetes. Whether serum uric acid is involved in the pathogenesis of diabetic foot ulcer in female patients remains to be investigated.
[show abstract][hide abstract] ABSTRACT: In this work, a variety of new conjugated chromophores containing imino and hydroxyl groups are presented. Excited state intramolecular proton transfer (ESIPT) of these chromophores under one- and two-photon irradiation was surveyed. One-photon absorption spectra show the presence of internal hydrogen bond in the organic dyes containing ortho-hydroxyl group, while the corresponding dyes carrying para-hydroxyl group do not exhibit intramolecular H-bonding effect. In the most of aprotic and protic solvents, the extended chromophores bearing ortho-hydroxyl group exhibit well-separated dual emission bands with large Stokes shift (ca. 160 nm), as contrast, the molecules containing para-hydroxyl group exhibit only single band with normal Stokes shift (ca. 50 nm). Two-photon absorption (TPA) induced competitive ESIPT emission can also be observed by near-infrared (near-IR) femtosecond laser to the molecules carrying ortho-hydroxyl group. The experiments show that the molecules carrying ortho-hydroxyl group are able to undergo ESIPT under one- and two-photon excitation, while the molecules containing para-hydroxyl groups do not exhibit such properties. 2-((3′,4′-Dimethoxyl-phenylethyleneyl-phenyl-4-ylimino)methyl)phenol (C1) and 2-((3′,4′,5′- trimethoxyl-phenylethyleneyl-phenyl-4-ylimino)methyl)phenol (C3) exhibit regular and selective response to Zn2+ in DMF. The molecular modeling was further performed to analyze ESIPT occurrence theoretically.
[show abstract][hide abstract] ABSTRACT: A variety of linear and side-chained p-nitrostilbene derivatives with various numbers of bromine atoms were prepared to survey the crystal structural properties, the photoluminescence, and heavy atom effect on the singlet oxygen generation by two-photo absorption (TPA). Single crystals of 4-nitro-4′-(4″-bromo-phenyl-methyl-oxy)-diphenylethylene (C2), 4-nitro-4′-(3″,5″-dibromo-phenyl-methyl-oxy)-diphenylethylene (C3), 4-nitro-4′-(2′,3″,4′,5″,6″-pentabromo-phenyl-methyl-oxy)-diphenylethylene (C4) were obtained, and the structural characteristics were analyzed by X-ray diffraction. One- and two-photon optical properties of the photosensitizers are shown dependence on the numbers of substituted bromine atoms. While TPA cross-sections of the photosensitizers are diminished more considerably, singlet oxygen quantum yields of the photosensitizers are enhanced at some extents by the substituted bromine atoms. Side-chained photosensitizers display correspondingly higher singlet oxygen quantum yields and larger TPA cross-sections than the molecules with single bromine-substituted aromatic segment. Molecular modeling was also performed to reveal the fundamental reasons of the experimental observation. Photooxidation reaction of singlet oxygen with some substrates was employed to confirm singlet oxygen generation under one- and two-photon irradiation.
[show abstract][hide abstract] ABSTRACT: In diabetic patients complicated with colorectal cancer (CRC), metformin treatment was reported to have diverse correlation with CRC-specific mortality. In laboratory studies, metformin was reported to affect the survival of cancer stem cells (CSCs) in breast and pancreatic cancers and glioblastoma. Although cscs play a critical role in the resistance to 5-fluorouracil (5-FU) chemotherapy in CRC patients, the effect of metformin on cscs in CRC patients and the synergistic effect of metformin in combination with 5-FU on cscs are not reported. In the present study pathological examinations were performed in 86 CRC patients complicated with type 2 DM who had been divided into a metformin group and a non-metformin group. Comparisons regarding pathological type, incidence of metastasis, expression of CD133 and β-catenin were conducted between the two groups. We explored the synergistic effects of metformin in combination with 5-FU on the proliferation, cell cycle, apoptosis and the proportion of CD133+ cscs of SW620 human colorectal cancer cell lines. The results show that metformin treatment had reverse correlations with the proportion of patients with poorly differentiated adenocarcinoma, the proportion of CD133+ cscs in CRC patients with type 2 DM. Metformin enhanced the antiproliferative effects of 5-FU on CD133+ cscs in SW620 cells. These findings provide an important complement to previous study. Inhibition of the proliferation of CD133+ cscs may be a potential mechanism responsible for the association of metformin use with improved CRC outcomes in CRC patients with type 2 diabetes.
PLoS ONE 01/2013; 8(11):e81264. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: To investigate the relationship between the expression of leptin and its long-form receptor, OB-RL, and wound healing in diabetic foot ulcers. Biopsies from 10 patients with diabetic foot ulcers (DU group), 10 with non-diabetic foot ulcers (NDU group), and 10 with normal skin (normal control, NC group) were examined. Leptin and OB-RL mRNA and protein levels were assessed using RT-PCR and immunohistochemistry analyses, respectively. The cuticle thickness was significantly greater, and the epidermal layer was significantly lesser in the DU and NDU groups. Leptin protein expression was significantly higher in the DU and NDU than NC group (P < 0.001), whereas OB-RL mRNA and protein expressions were significantly lower in the DU group and significantly higher in the NDU group (P < 0.001). Diabetic foot ulcer duration was negatively correlated with OB-RL protein expression (ρ = -0.671, P = 0.034). Decreased OB-RL may result in reduced leptin signaling in diabetic foot ulcers. Further studies are required to determine whether OB-RL levels are related to the prognosis of diabetic foot ulcers, as well as to explore the use of leptin or mimetics for promoting ulcer healing.
[show abstract][hide abstract] ABSTRACT: The generation of myelinating cells from multipotential neural stem cells in the CNS requires the initiation of specific gene expression programs in oligodendrocytes (OLs). We reasoned that microRNAs (miRNAs) could play an important role in this process by regulating genes crucial for OL development. Here we identified miR-7a as one of the highly enriched miRNAs in oligodendrocyte precursor cells (OPCs), overexpression of which in either neural progenitor cells (NPCs) or embryonic mouse cortex promoted the generation of OL lineage cells. Blocking the function of miR-7a in differentiating NPCs led to a reduction in OL number and an expansion of neuronal populations simultaneously. We also found that overexpression of this miRNA in purified OPC cultures promoted cell proliferation and inhibited further maturation. In addition, miR-7a might exert the effects just mentioned partially by directly repressing proneuronal differentiation factors including Pax6 and NeuroD4, or proOL genes involved in oligodendrocyte maturation. These results suggest that miRNA pathway is essential in determining cell fate commitment for OLs and thus providing a new strategy for modulating this process in OL loss diseases.
Molecular biology of the cell 06/2012; 23(15):2867-78. · 5.98 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aim of the present study was to evaluate the active and passive mechanical properties and wall collagen and elastin contents of mesenteric small arteries (MSAs) isolated from rats of 28-day simulated microgravity (SUS), countermeasure [S + D: SUS plus 1 h/d -G(x) to simulate intermittent artificial gravity (IAG)] and control (CON) groups. Three mechanical parameters were calculated: the overall stiffness (β), circumferential stress (σ(θ))-strain (ε(θ)) relationship and pressure-dependent incremental elastic modulus (E(inc,p)). Vessel wall collagen and elastin percentage were quantified by electron microscopy. The results demonstrate that the active mechanical behavior of MSAs differs noticeably among the three groups: the active stress-strain curve of SUS vessels is very close to the passive curve, whereas the active σ(θ)-ε(θ) curves of CON and S + D vessels are shifted leftward and display a parabolic shape, indicating that for MSAs isolated from S + D, but not those from SUS rats, the pressure-induced myogenic constriction can effectively stiffen the vessel wall as the CON vessels. The passive mechanical behavior of MSAs does not show significant differences among the three groups. However, the percentage of collagen is decreased in the wall of SUS and S + D compared with CON vessels in the following order: SUS < S + D < CON. Thus, the relationship between passive mechanical behavior and compositional changes may be complex and yet depends on factors other than the quantity of collagen and elastin. These findings have provided biomechanical data for the understanding of the mechanism of postflight orthostatic intolerance and its gravity-based countermeasure.
Sheng li xue bao: [Acta physiologica Sinica] 04/2012; 64(2):107-20.
[show abstract][hide abstract] ABSTRACT: The present study was designed to test the hypothesis that a medium-term simulated microgravity can induce region-specific remodeling in large elastic arteries with their innermost smooth muscle (SM) layers being most profoundly affected. The second purpose was to examine whether these changes can be prevented by a simulated intermittent artificial gravity (IAG). The third purpose was to elucidate whether vascular local renin-angiotensin system (L-RAS) plays an important role in the regional vascular remodeling and its prevention by the gravity-based countermeasure. This study consisted of two interconnected series of in-vivo and ex-vivo experiments. In the in-vivo experiments, the tail-suspended, hindlimb unloaded rat model was used to simulate microgravity-induced cardiovascular deconditioning for 28 days (SUS group); and during the simulation period, another group was subjected to daily 1-hour dorso-ventral (-G(x)) gravitation provided by restoring to normal standing posture (S + D group). The activity of vascular L-RAS was evaluated by examining the gene and protein expression of angiotensinogen (Ao) and angiotensin II receptor type 1 (AT1R) in the arterial wall tissue. The results showed that SUS induced an increase in the media thickness of the common carotid artery due to hypertrophy of the four SM layers and a decrease in the total cross-sectional area of the nine SM layers of the abdominal aorta without significant change in its media thickness. And for both arteries, the most prominent changes were in the innermost SM layers. Immunohistochemistry and in situ hybridization revealed that SUS induced an up- and down-regulation of Ao and AT1R expression in the vessel wall of common carotid artery and abdominal aorta, respectively, which was further confirmed by Western blot analysis and real time PCR analysis. Daily 1-hour restoring to normal standing posture over 28 days fully prevented these remodeling and L-RAS changes in the large elastic arteries that might occur due to SUS alone. In the ex-vivo experiments, to elucidate the important role of transmural pressure in vascular regional remodeling and differential regulation of L-RAS activity, we established an organ culture system in which rat common carotid artery, held at in-vivo length, can be perfused and pressurized at varied flow and pressure for 7 days. In arteries perfused at a flow rate of 7.9 mL/min and pressurized at 150 mmHg, but not at 0 or 80 mmHg, for 3 days led to an augmentation of c-fibronectin (c-FN) expression, which was also more markedly expressed in the innermost SM layers, and an increase in Ang II production detected in the perfusion fluid. However, the enhanced c-FN expression and increased Ang II production that might occur due to a sustained high perfusion pressure alone were fully prevented by daily restoration to 0 or 80 mmHg for a short duration. These findings from in-vivo and ex-vivo experiments have provided evidence supporting our hypothesis that redistribution of transmural pressures might be the primary factor that initiates region-specific remodeling of arteries during microgravity and the mechanism of IAG is associated with an intermittent restoration of the transmural pressures to their normal distribution. And they also provide support to the hypothesis that L-RAS plays an important role in vascular adaptation to microgravity and its prevention by the IAG countermeasure.
Sheng li xue bao: [Acta physiologica Sinica] 02/2012; 64(1):14-26.
[show abstract][hide abstract] ABSTRACT: This paper presents experimental and theoretical investigations into excited-state intramolecular proton transfer (ESIPT) in new chromophores with hydroxyl and imino groups under one- and two-photon excitation. The results show that internal hydrogen bonding exhibits a remarkable influence on the maximum absorption wavelength of 2-[(4'-N,N-diethylaminodiphenylethylene-4-ylimino)methyl]phenol (C1) and 2-[(4'-methoxyl-diphenylethylene-4-ylimino)methyl]phenol (C3). Compounds C1 and C3 exhibit well-separated dual fluorescence emission bands under one- and two-photon excitation. The second fluorescence peaks of C1 and C3 are characterized by much larger Stokes shift than the first normal peaks (ca. 140 vs. 30 nm). 4-[(4'-N,N-Diethylaminodiphenylethylene-4-ylimino)methyl]phenol (C2) and 4-[(4'-methoxyldiphenylethylene-4-ylimino)methyl]phenol (C4) display single emission bands with small Stokes shifts (ca. 30 nm) in various solvents under one- and two-photon excitation. Furthermore, the first emission maxima of C1 and C3 are almost identical to the maximum fluorescence emission wavelengths of C2 and C4, respectively. These results show that C1 and C3 can undergo ESIPT via a reasonable six-membered ring, while there is no ESIPT in C2 and C4 under one- and two-photon excitation. Compounds C1 and C2 have larger two-photon absorption cross-sections under various near-infrared laser frequencies tuned from 700 to 880 nm. Molecular geometry optimization of the phototautomers (enol and keto) was performed to analyze the experimental results. The possibility of using these chromophores for metal ions as chemosensors of was thoroughly investigated. In DMF C3 exhibits excellent sensing responses to Zn(2+) and Fe(3+) ions through a greatly increased greatly and a largely reduced emission, respectively. In methanol disappearance of ESIPT emission with added Zn(2+) ions confirms its existence. The binding constants of C3 with Zn(2+) and Fe(3+) ions in DMF are also estimated.
[show abstract][hide abstract] ABSTRACT: Data on many predictors of hypothalamic-pituitary axis dysfunction associated with childhood craniopharyngioma (CP) are rather inconsistent, probably reflecting the variable but as yet unclarified growth pattern of these tumours. The aim of this study was to define the determinative role of tumour growth pattern on hypothalamic-pituitary axis function and outcomes for childhood CPs.
The authors retrospectively analysed the records of 81 consecutive children with primary CP who underwent a uniform treatment paradigm of attempted radical resection performed by a single surgeon. The patients were divided into two subgroups based on tumour location and growth patterns: group A (infra-diaphragmatic sellar tumours: 34 cases) and group B [third ventricular floor (3rd VF) tumours: 47 cases]. The children's pre- and postsurgical endocrinological and hypothalamic disturbances were compared. Pituitary function and hypothalamic statues were quantitatively assessed using classification systems proposed in the previous studies.
Preoperative pituitary function was more severely compromised in patients in group A than those in group B and deteriorated significantly following resection in both groups. (Average pituitary function scores increased from 2·19 ± 0·83 to 3·31 ± 0·74, P < 0·001). At the last follow-up, children with 3rd VF tumours had more prevalent weight gain (median body mass index: 23·1 kg/m(2) in group B vs 19·7 kg/m(2) in group A, P < 0·001) and increased hypothalamic dysfunction (average hypothalamic status scores: 2·04 ± 0·97 in group B vs 1·29 ± 0·57 in group A, P < 0·001). Children with 3rd VF tumours had a significantly lower probability of recurrence-free survival than those with sellar tumours (at 5 years: 74%vs 49%, respectively; at 10 years: 66%vs 32%, respectively; P = 0·02).
Substantial differences in the outcome of childhood CP with different tumour growth patterns and locations were found, which suggested that diverse therapeutic considerations, especially endocrinological substitution, might be emphasized.
[show abstract][hide abstract] ABSTRACT: To investigate the cellular memory of previous high glucose exposure in rat islet cell line (INS-1) and explore the possible mechanism.
INS-1 cells were exposed to a high glucose (33.3 mmol/L) culture for 48 h followed by further culture in the presence of 11.1 mmol/L glucose in the culture medium for 3 or 5 days. The levels of bax and caspase-3 mRNA were measured by real-time PCR, the production of reactive oxygen species (ROS) was assayed using the dihydroethidium probe, and the cell viability was detected by MTT assay.
High glucose exposure of the cells for 48 h resulted in significantly increased ROS production and bax and caspase-3 mRNA expressions and lowered cell viability (P<0.001). In cells cultured in 11.1 mmol/L glucose following previous high glucose exposure, the ROS production and bax and caspase-3 mRNA expressions still maintained the high levels (P<0.05) while the cell viability remained significantly lower than the control cells (P<0.001).
High glucose causes persistent changes in cell viability and apoptosis-related gene expressions even after recovery of normoglycemia, the mechanism of which is probably related to increased ROS production.
Nan fang yi ke da xue xue bao = Journal of Southern Medical University 04/2011; 31(4):682-5.
[show abstract][hide abstract] ABSTRACT: This article presents a comprehensive theoretical investigation of excited state intramolecular proton transfer (ESIPT) for some newly-designed diphenylethylene derivatives containing 2-(2-hydroxy-phenyl)-benzotriazole moiety with various substituted groups. The calculation shows the structural parameters and Mulliken charges of phototautomers enol (E) and keto (K) of these compounds exhibit no or tiny changes from S(0) to S(1). The calculated results suggest that HOMO and LUMO + 1 of the compounds displays excellent overlapping nature, and thus the absorption and emission could be from the electron transition of HOMO→LUMO + 1. The electron density distribution in the frontier orbital of E and K are influenced remarkably by various substituted groups in S(0) and S(1) states. Electron density distribution deficiency in 2-(2-hydroxy-phenyl)-benzotriazole part is observed in L + 1 for these derivatives. The calculation also suggests the potential energy curves of ESIPT are shown to be a strong relationship with electron donor-acceptor groups. The absorption spectra, normal emission spectra and ESIPT spectra of the derivatives were also calculated.
Journal of Fluorescence 03/2011; 21(4):1721-8. · 1.79 Impact Factor
[show abstract][hide abstract] ABSTRACT: To evaluate the effect of short-term intensive therapy on blood glucose control, BETA-cell function, and blood lipid levels in newly diagnosed type 2 diabetic patients.
Out-patients with newly diagnosed type 2 diabetic patients were enrolled for intensive treatment with sulfonylureas and metformin for 12 weeks, and the therapeutic effect was evaluated.
After the intensive treatment, FPG, 2 hPG, and HbA1c decreased significantly (P<0.01); HOMA-IR decreased and HOMA-B increased significantly (P<0.01), and TG, CHOL, LDL decreased significantly (P<0.01) after the treatment.
Short-term intensive treatment with glimepiride combined with metformin is safe and effective in newly diagnosed type 2 diabetic patients with HbA1c>9%.
Nan fang yi ke da xue xue bao = Journal of Southern Medical University 03/2011; 31(3):564-6.
[show abstract][hide abstract] ABSTRACT: Genus Wautersia is a Gram-negative bacterium that has rarely been associated with human infections abroad, and is firstly reported in home. We report a case of sepsis caused by Wautersia species, which was separated from blood and bone marrows.
Nan fang yi ke da xue xue bao = Journal of Southern Medical University 03/2011; 31(3):559-60.
[show abstract][hide abstract] ABSTRACT: Some studies suggest that the calcium channels and rennin-angiotensin system (RAS) play pivotal roles in the region-specific vascular adaptation due to simulated weightlessness. This study was designed to clarify if angiotensin II (Ang II) was involved in the adaptational change of the L-type calcium channel (Ca(L)) in the cerebral arterial vascular smooth muscle cells (VSMCs) under simulated weightlessness. Tail suspension (SUS) for 3 d was used to simulate immediate early cardiovascular changes to weightlessness. Then VSMCs in cerebral basilar artery were enzymatically isolated using papain, and Ca(L) current (barium instead of calcium as current carrier) in VSMCs was measured by whole-cell patch-clamp techniques. The results showed that 3-day simulated weightlessness significantly increased current density of Ca(L). However, I-V relationships of normalized peak current densities and steady-state activation curves of Ca(L) were not affected by simulated weightlessness. Although Ang II significantly increased current densities of Ca(L) in both SUS and control rats, the increase of Ca(L) current density in SUS rats was much more than that in control rats. These results suggest that 3-day simulated weightlessness induces the adaptational change of Ca(L) in cerebral VSMCs including increased response to Ang II, indicating that Ang II may play an important role in the adaptational change of cerebral arteries under microgravity.
Sheng li xue bao: [Acta physiologica Sinica] 02/2011; 63(1):81-8.
[show abstract][hide abstract] ABSTRACT: Cancer stem cells (CSCs) play an important role in the development and recurrence of malignant tumors including glioma. Notch signaling, an evolutionarily conserved pathway mediating direct cell-cell interaction, has been shown to regulate neural stem cells (NSCs) and glioma stem cells (GSCs) in normal neurogenesis and pathological carcinogenesis, respectively. However, how Notch signaling regulates the proliferation and differentiation of GSCs has not been well elucidated.
We isolated and cultivate human GSCs from glioma patient specimens. Then on parallel comparison with NSCs, we inhibited Notch signaling using γ-secretase inhibitors (GSI) and assessed the potential functions of Notch signaling in human GSCs.
Similar to the GSI-treated NSCs, the number of the primary and secondary tumor spheres from GSI-treated GSCs decreased significantly, suggesting that the proliferation and self-renewal ability of GSI-treated GSCs were attenuated. GSI-treated GSCs showed increased differentiation into mature neural cell types in differentiation medium, similar to GSI-treated NSCs. Next, we found that GSI-treated tumor spheres were composed of more intermediate progenitors instead of CSCs, compared with the controls. Interestingly, although inhibition of Notch signaling decreased the ratio of proliferating NSCs in long term culture, we found that the ratio of G2+M phase-GSCs were almost undisturbed on GSI treatment within 72 h.
These data indicate that like NSCs, Notch signaling maintains the patient-derived GSCs by promoting their self-renewal and inhibiting their differentiation, and support that Notch signal inhibitor GSI might be a prosperous candidate of the treatment targeting CSCs for gliomas, however, with GSI-resistance at the early stage of GSCs cell cycle.
[show abstract][hide abstract] ABSTRACT: This paper describes a new fluorescent family of branched dyes containing benzophenone unit including 4-N, N-diphenylamino-4'-phenacyl-stilbene (C1), 4,4'-di(4-benzoylphenylethylene)yl-triphenylamine (C2) and 4,4',4″-tri(4-benzoylphenylethylene)yl-triphenylamine (C3). Benzophenone part is coupled with core through C-C double bond. The chemical structures of the derivatives are characterized with (1)H and (13)C nuclear magnetic resonance and elemental analysis. Strong π-π stacking interactions are discovered with the analysis of the X-ray crystallographic data of C1. The absorption maxima and emission maxima of the derivatives exhibit gradual bathochromic shift from C1 to C3. The optical density of C1, C2 and C3 are shown to be related to the number of branches. The changes of dipole moments between the excited and ground states for C1, C2 and C3 were estimated to be 4.356, 8.091 and 8.479 Derby, respectively by Lippert equation, confirming that the internal charge transfer (ICT) dominates the process of excited singlet state. The possibility as fluorescence probes of the derivatives on the estimation of what region of micelles interacting with samples was evaluated.
Journal of Fluorescence 01/2011; 21(1):149-59. · 1.79 Impact Factor
[show abstract][hide abstract] ABSTRACT: o-hydroxyphenyl-triazine derivatives with formyl substituents were surveyed for the excited state intramolecular proton transfer
(ESIPT). The occurrence of ESIPT was confirmed by well-separated emission bands for the derivatives. A low energy change from
enol to keto in the excited state explains ESIPT for the derivatives.
Chinese Science Bulletin 01/2011; 56(14):1457-1460. · 1.32 Impact Factor
[show abstract][hide abstract] ABSTRACT: Fibroblasts are important to host defence and immunity, can also as initiators of inflammation as well. As the endogenous "braking signal", Lipoxins can regulate anti-inflammation and the resolution of inflammation. We investigated the effect of lipoxinA(4) on the expression of cyclooxygenase-2 in lipopolysaccharide-stimulated lung fibroblasts. We demonstrated that the expression of cyclooxygenase-2 protein was significantly increased and peaked initially at 6 hours, with a second increase, with maximal levels occurring 24 hours after lipopolysaccharide challenge. ProstaglandinE(2) levels also peaked at 6 hours, and prostaglandinD(2) levels were increased at both 6 and 24 hours. Exogenous lipoxinA(4) inhibited the first peak of cyclooxygenase-2 expression as well as the production of prostaglandinE(2) induced by lipopolysaccharide in a dose-dependent manner. In contrast, exogenous lipoxinA(4) increased the second peak of cyclooxygenase-2 expression as well as the production of prostaglandinD(2) induced by lipopolysaccharide in a dose-dependent manner. LipoxinA(4) receptor mRNA expression was markedly stimulated by lipopolysaccharide but inhibited by lipoxinA(4). We present evidence for a novel biphasic role of lipoxinA(4) on the expression of cyclooxygenase-2 in lipopolysaccharide-stimulated lung fibroblasts, whereby LXA(4) has an anti-inflammatory and proresolving activity in lung fibroblasts following LPS stimulation.
Mediators of Inflammation 01/2011; 2011:745340. · 3.88 Impact Factor