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The fish oil ingredient, docosahexaenoic acid, activates cytosolic phospholipase A 2 via GPR120 receptor to produce prostaglandin E 2 and plays an anti‐inflammatory role in macrophages
Author(s) -
Liu Yueqin,
Chen LiYuan,
Sokolowska Milena,
Eberlein Michael,
Alsaaty Sara,
MartinezAnton Asuncion,
Logun Carolea,
Qi HaiYan,
Shelhamer James H.
Publication year - 2014
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12296
Subject(s) - docosahexaenoic acid , phospholipase a2 , gpr120 , arachidonic acid , prostaglandin e2 receptor , lipid signaling , prostaglandin e2 , prostaglandin , protein kinase a , receptor , biology , biochemistry , chemistry , endocrinology , kinase , agonist , g protein coupled receptor , fatty acid , polyunsaturated fatty acid , enzyme
Summary Docosahexaenoic acid (DHA) is one of the major ingredients of fish oil and has been reported to have anti‐inflammatory properties mediated through the GPR120 receptor. Whether cytosolic phospholipase A 2 ( cPLA 2 ) and lipid mediators produced from cPLA 2 activation are involved in the anti‐inflammatory role of DHA in macrophages has not been reported. We report here that DHA and the GPR120 agonist, GW9508, activate cPLA 2 and cyclooxygenase 2 (COX‐2), and cause prostaglandin E 2 (PGE 2 ) release in a murine macrophage cell line RAW264.7 and in human primary monocyte‐derived macrophages. DHA and GW9508 activate cPLA 2 via GPR120 receptor, G protein G α q and scaffold protein β ‐arrestin 2. Extracellular signal‐regulated kinase 1/2 activation is involved in DHA‐ and GW9508‐induced cPLA 2 activation, but not p38 mitogen‐activated protein kinase. The anti‐inflammatory role of DHA and GW9508 is in part via activation of cPLA 2 , COX‐2 and production of PGE 2 as a cPLA 2 inhibitor or a COX‐2 inhibitor partially reverses the DHA‐ and GW9508‐induced inhibition of lipopolysaccharide‐induced interleukin‐6 secretion. The cPLA 2 product arachidonic acid and PGE 2 also play an anti‐inflammatory role. This effect of PGE 2 is partially through inhibition of the nuclear factor‐κB signalling pathway and through the EP4 receptor of PGE 2 because an EP4 inhibitor or knock‐down of EP4 partially reverses DHA inhibition of lipopolysaccharide‐induced interleukin‐6 secretion. Hence, DHA has an anti‐inflammatory effect partially through induction of PGE 2 .