Details

Autor(en) / Beteiligte

• Wu, Sheng-Hua
• Liao, P.-Y.
• Dong, L.
• Chen, Z.-Q.

Titel

Signal pathway involved in inhibition by lipoxin A4 of production of interleukins induced in endothelial cells by lipopolysaccharide

Ist Teil von

• Inflammation research, 2008-09, Vol.57 (9), p.430-437

Ort / Verlag

Basel: SP Birkhäuser Verlag Basel

Erscheinungsjahr

2008

Quelle

SpringerLink Journals - AutoHoldings

Beschreibungen/Notizen

• . Objective and design: We examine whether lipoxin A 4 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-1β, 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-κ B (NF-κB) and activator protein-1(AP-1). The blockade of p38 MAPK, p42/44 MAPK, PI3-K, NF-κB or AP-1 partially inhibited production of IL-1β, IL-6 and IL-8 stimulated by LPS, respectively. LXA 4 significantly inhibited LPS-stimulated secretion of protein and expressions of mRNA of IL-1β, IL-6 and IL-8, activation of p38 MAPK, p42/44 MAPK, PI3-K, NF-κB and AP-1 but not MyD88 in PMVEC. Conclusions: LXA 4 inhibits synthesis of IL-1β, IL-6 and IL-8 in PMVEC and this antagonism is related to PI3-K, p38 and p42/44 MAPK, NF-κB and AP-1 pathway-dependent signal transduction.