PMID- 21575454 OWN - NLM STAT- MEDLINE DCOM- 20120524 LR - 20110517 IS - 0529-567X (Print) IS - 0529-567X (Linking) VI - 46 IP - 3 DP - 2011 Mar TI - [Effect of lipoxin A(4) on lipopolysaccharide-induced endothelial hyperpermeability in human umbilical vein endothelial cell]. PG - 199-204 AB - OBJECTIVE: To explore whether lipoxin A(4) (LXA(4))could prevent lipopolysaccharide (LPS)-induced human umbilical vein endothelial cells (HUVEC) monolayer hyperpermeability and its possible mechanism. METHODS: Human umbilical cords were obtained from women with normal pregnancy immediately after delivery from Tongji Hospital Affiliated of Tongji Medical College. Primary HUVEC were isolated from umbilical veins and subcultured, then, HUVEC were divided into four groups:control group; LPS group (10 mg/L of LPS); LPS + LXA(4) group(10 mg/L of LPS and 100 nmol/L of LXA(4)); LPS + LXA(4) + BOC-2 group [10 micromol/L of BOC-2, an effective antagonist of formyl peptide receptor like 1 (FPRL-1)]. All expriments were performed after cells were treated for 24 hours. Endothelial permeability was measured by fluorescein isothiocyan-ate labelled bovine serum albumin (FITC-BSA) clearance across the monolayer; tumor necrosis factor alpha (TNF-alpha) mRNA and secretion were detected by reverse transcriplase (RT)-PCR and ELISA assay respectively, and nuclear factor kappaB (NF-kappaB) protein change was determined by western blot. RESULTS: (1) LPS induced a significant increase in the permeability [Pa value of LPS group was (183.1 +/- 1.7)%], while co-administrating with LXA(4) obviously attenuated this LPS-induced hyperpermeability, Pa value of LPS + LXA(4) group was (103.1 +/- 2.2)%, LPS + LXA(4) + BOC-2 group was (162.2 +/- 2.8)%, control group was 100%, the permeability of HUVEC monolayer was significantly increased by LPS which was (83.1 +/- 1.7)% of control (P < 0.01), however, it was notably inhibited by LXA(4) (P < 0.05); the blockade of FPRL-1 could attenuate the effect of LXA(4), that is, there was no difference between the LPS + LXA(4) + BOC-2 group and the LPS group. (2) After treatment with different concentration of LPS(0, 0.1, 1, 10 mg/L), the mRNA expressions of TNF-alpha were increased (1.11 +/- 0.11, 1.27 +/- 0.03, 1.60 +/- 0.06, 1.82 +/- 0.04, respectively), compared with the control group, at the concentration of 1, 10 mg/L LPS, the difference was statistically significant (P < 0.05). (3) The increased levels of NF-kappaB and inflammatory mediator TNF-alpha in the LPS group were both inhibited by LXA(4). Levels of NF-kappaB protein and TNF-alpha mRNA secretion in LPS treated group (0.53 +/- 0.06 and 0.81 +/- 0.09, respectively) were both inhibited by LXA(4)(0.19 +/- 0.05 and 0.41 +/- 0.07, respectively, and both had significant difference, P < 0.05). (4) Levels of TNF-alpha in HUVEC culture medium of LPS group [(31.94 +/- 0.01) ng/L] was significantly higher than the control group [(18.17 +/- 0.03) ng/L, P < 0.05], LPS + LXA(4) group [(15.72 +/- 0.07) ng/L] was significantly lower than the LPS group (P < 0.05). CONCLUSION: Our findings demonstrated that LXA(4) could prevent the endothelial cell hyperpermeability induced by LPS in HUVEC under which the possible mechanism was through inhibiting the expression of NF-kappaB and its related cytokines through receptor-dependent. FAU - Pang, Hua-yan AU - Pang HY AD - Department of Obstetrics and Gynecology, First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, China. FAU - Huang, Yin-ping AU - Huang YP FAU - Liu, Zhong-jie AU - Liu ZJ FAU - Yi, Pan AU - Yi P FAU - Gong, Jian-ming AU - Gong JM FAU - Hao, Hua AU - Hao H FAU - Wu, Ping AU - Wu P FAU - Zhou, Jie AU - Zhou J FAU - Cai, Lei AU - Cai L FAU - Huang, Yan-jun AU - Huang YJ FAU - Ye, Du-yun AU - Ye DY FAU - Wang, Zhen-huan AU - Wang ZH LA - chi PT - English Abstract PT - Journal Article PL - China TA - Zhonghua Fu Chan Ke Za Zhi JT - Zhonghua fu chan ke za zhi JID - 16210370R RN - 0 (Lipopolysaccharides) RN - 0 (Lipoxins) RN - 0 (NF-kappa B) RN - 0 (RNA, Messenger) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (lipoxin A4) SB - IM MH - Capillary Permeability/*drug effects MH - Cells, Cultured MH - Female MH - Human Umbilical Vein Endothelial Cells/*drug effects/metabolism MH - Humans MH - Lipopolysaccharides/adverse effects/antagonists & inhibitors MH - Lipoxins/administration & dosage/*pharmacology MH - NF-kappa B/genetics/*metabolism MH - Pregnancy MH - RNA, Messenger/genetics/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Tumor Necrosis Factor-alpha/genetics/metabolism EDAT- 2011/05/18 06:00 MHDA- 2012/05/25 06:00 CRDT- 2011/05/18 06:00 PHST- 2011/05/18 06:00 [entrez] PHST- 2011/05/18 06:00 [pubmed] PHST- 2012/05/25 06:00 [medline] PST - ppublish SO - Zhonghua Fu Chan Ke Za Zhi. 2011 Mar;46(3):199-204.