Attenuation of LPS-induced cyclooxygenase-2 and inducible NO synthase expression by lysophosphatidic acid in macrophages:

Innate Immunity

Han-YuanChien¹ 

关键词: Cyclooxygenase-2;    inducible NO synthase;    inflammation;    lipopolysaccharide;    lysophosphatidic acid;   

DOI  :  10.1177/1753425915576345

学科分类：生物科学（综合）

来源: Sage Journals

【 摘 要 】

LPS can activate the inflammatory cascades by inducing various inflammatory mediators, such as prostaglandin E2 (PGE2) resulting from cyclooxygenase-2 (COX-2), and NO produced by inducible NO synthase (iNOS). Lysophosphatidic acid (LPA) has been demonstrated to participate in inflammation. This study aimed to clarify the impact and the involving mechanisms of LPA on LPS-incurred inflammation in macrophages. First, LPA appeared to attenuate LPS-induced protein and mRNA expression of COX-2 and iNOS genes, as well as production of PGE2 and NO. By using selective inhibitors targeting various signaling players, the inhibitory G protein alpha subunit (Gαi) seemed to be involved in the effect of LPA; p38, ERK and NF-κB were involved in the LPS-mediated COX-2/PGE2 pathway; and p38, JNK, phosphoinositide-3-kinase and NF-κB were involved in the LPS-mediated iNOS/NO pathway. LPA was able to diminish LPS-induced phosphorylation of p38 and Akt, as well as NF-κB p65 nuclear translocation. By utilization of inhibitors o...

【 授权许可】

CC BY