PMID- 18777114 OWN - NLM STAT- MEDLINE DCOM- 20090113 LR - 20101118 IS - 1023-3830 (Print) IS - 1023-3830 (Linking) VI - 57 IP - 9 DP - 2008 Sep TI - Signal pathway involved in inhibition by lipoxin A(4) of production of interleukins induced in endothelial cells by lipopolysaccharide. PG - 430-7 LID - 10.1007/s00011-008-7147-1 [doi] AB - OBJECTIVE AND DESIGN: We examine whether lipoxin A(4) (LXA(4)) inhibits production of interleukins (ILs) in endothelial cells and what signal pathway might participate in the actions of LXA(4). METHODS: Cultured pulmonary microvascular endothelial cells (PMVEC) were treated with lipopolysaccharide (LPS), with or without preincubation with LXA(4). RESULTS: The results showed that LPS induced production of IL-1beta, IL-6 and IL-8 in rat PMVEC, upregulated the expressions of myeloid differentiation factor 88 (MyD88), phosphorylated p38 and p42/44 mitogen-activated protein kinase (MAPK), phosphorylated phosphoinositide 3-kinase (PI3-K), DNA-binding activities of nuclear factor-kappa B (NF-kappaB) and activator protein-1(AP-1). The blockade of p38 MAPK, p42/44 MAPK, PI3-K, NF-kappaB or AP-1 partially inhibited production of IL-1beta, IL-6 and IL-8 stimulated by LPS, respectively. LXA(4) significantly inhibited LPS-stimulated secretion of protein and expressions of mRNA of IL-1beta, IL-6 and IL-8, activation of p38 MAPK, p42/44 MAPK, PI3-K, NF-kappaB and AP-1 but not MyD88 in PMVEC. CONCLUSIONS: LXA(4) inhibits synthesis of IL-1beta, IL-6 and IL-8 in PMVEC and this antagonism is related to PI3-K, p38 and p42/44 MAPK, NF-kappaB and AP-1 pathway-dependent signal transduction. FAU - Wu, Sheng-Hua AU - Wu SH AD - Department of Pediatrics, Central Laboratory, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, People's Republic of China. FAU - Liao, P-Y AU - Liao PY FAU - Dong, L AU - Dong L FAU - Chen, Z-Q AU - Chen ZQ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Switzerland TA - Inflamm Res JT - Inflammation research : official journal of the European Histamine Research Society ... [et al.] JID - 9508160 RN - 0 (Interleukins) RN - 0 (Lipopolysaccharides) RN - 0 (Lipoxins) RN - 0 (Myd88 protein, rat) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (NF-kappa B) RN - 0 (RNA, Messenger) RN - 0 (lipoxin A4) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) SB - IM MH - Animals MH - Endothelial Cells/*drug effects/immunology MH - Extracellular Signal-Regulated MAP Kinases/metabolism MH - Inflammation/drug therapy MH - Interleukins/*biosynthesis MH - Lipopolysaccharides/*pharmacology MH - Lipoxins/*pharmacology MH - Male MH - Myeloid Differentiation Factor 88/metabolism MH - NF-kappa B/metabolism MH - Phosphatidylinositol 3-Kinases/metabolism MH - RNA, Messenger/analysis MH - Rats MH - Rats, Wistar MH - *Signal Transduction MH - p38 Mitogen-Activated Protein Kinases/metabolism EDAT- 2008/09/09 09:00 MHDA- 2009/01/14 09:00 CRDT- 2008/09/09 09:00 PHST- 2008/09/09 09:00 [pubmed] PHST- 2009/01/14 09:00 [medline] PHST- 2008/09/09 09:00 [entrez] AID - 10.1007/s00011-008-7147-1 [doi] PST - ppublish SO - Inflamm Res. 2008 Sep;57(9):430-7. doi: 10.1007/s00011-008-7147-1.