Involvement of p38 and p42/44 MAP kinases and protein kinase C in the interferon-γ and interleukin-1α-induced phosphorylation of 85-kDa cytosolic phospholipase A₂ in primary human

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• 作者：Wu ; Tong ; Han ; Chang ; Shelhamer ; James H.
• 关键词：Interferon-γ ; Interleukin-1 ; Phospholipase A₂ ; MAP kinase ; Protein kinase C ; AA ; arachidonic acid ; AACOCF₃ ; arachidonyltrifluoromethyl ketone ; IFN-γ ; interferon-γ ; IL-1&#945 ; interleukin-1&#945 ; HELSS ; haloenol lacto
• 刊名：Cytokine
• 出版年：2004
• 出版时间：January 7, 2004
• 年：2004
• 卷：25
• 期：1
• 页码：11-20
• 全文大小：393 K

文摘

Interferon-γ (IFN-γ) and interleukin-1 (IL-1) play an important role in the modulation of acute and chronic airway inflammation. Both IFN-γ and IL-1 are known to increase the release of arachidonic acid (AA) from airway epithelial cells, suggesting that AA metabolites may mediate the cytokine-induced inflammation. This study was designed to examine the direct effect of IFN-γ and IL-&#945; on the phosphorylation of 85-kDa cytosolic phospholipase A₂ (cPLA₂) and AA release in primary normal human bronchial epithelial (NHBE) cells. Treatment with IFN-γ and IL-1&#945; for 15 min induced a rapid increase of AA release from NHBE cells, which was blocked by the cPLA₂ inhibitor MAFP (p<0.05) but not by the sPLA₂ inhibitor LY311727 or iPLA₂ inhibitor HELSS. Immunoprecipitation and Western blot analysis showed that both IFN-γ and IL-1&#945; induced a rapid phosphorylation of cPLA₂. The IFN-γ and IL-1&#945;-induced cPLA₂ phosphorylation and AA release in the NHBE cells were inhibited by the p38 MAP kinase (MAPK) inhibitor SB203580, p42/44 MAPK inhibitor PD98059 and protein kinase C (PKC) inhibitor bisindolylmaleimide I. These results demonstrate the involvement of p38 and p42/44 MAPKs as well as PKC in the IFN-γ and IL-1&#945;-induced cPLA₂ phosphorylation and AA release in human airway epithelial cells.