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  • Title: Signal pathway involved in inhibition by lipoxin A(4) of production of interleukins induced in endothelial cells by lipopolysaccharide.
    Author: Wu SH, Liao PY, Dong L, Chen ZQ.
    Journal: Inflamm Res; 2008 Sep; 57(9):430-7. PubMed ID: 18777114.
    Abstract:
    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.
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