Incorporation of sciadonic acid into cellular phospholipids reduces pro-inflammatory mediators in murine macrophages through NF-κB and MAPK signaling pathways.
Sciadonic acid (SCA; Δ5,11,14-20:3), a non-methylene-interrupted polyunsaturated fatty acid (NMIFA), can substitute for arachidonic acid (AA) and reduce prostaglandin E2 (PGE2) synthesis in macrophages. However, little is known about how SCA exerts its anti-inflammatory effects. The objectives of this study were to purify SCA from seeds of Podocarpus nagi and investigate mechanisms underlying the modulatory effects of SCA on inflammatory responses in murine RAW264.7 macrophages. We describe how high-purity SCA (>98%) can be obtained using argentated column chromatography. SCA was dose-dependently incorporated into cellular phospholipids, and increasing SCA incorporation correlated with decreases in the proportions of AA, total monounsaturated fatty acids (MUFA) and total saturated fatty acids (SFA). SCA decreased production of PGE2 (29%), nitric oxide (NO) (31%), interleukin-6 (IL-6) (34%) and tumor necrosis factor-α (TNF-α) (14%). The suppression of pro-inflammatory mediators was due, in part, to decreased expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). SCA incorporation suppressed nuclear factor-kappa B (NF-κB) translocation and phosphorylation of mitogen-activated protein kinases (MAPK), including extracellular signal-regulated kinase (ERK), p38 and c-Jun N-terminal kinase (JNK). These findings indicate that by altering the cellular fatty acid composition SCA can modulate the responsiveness of macrophages to LPS through inactivation of NF-κB and MAPK pathways.
Department of Radiation Oncology, Tao Yuan General Hospital, Tao-Yuan, Taiwan.
Szu-Jung
SJ
Chen
Wen-Cheng
WC
Huang
Tzu-Ting
TT
Yang
Jui-Hua
JH
Lu
Lu-Te
LT
Chuang
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001095:Arachidonic Acids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010743:Phospholipids / Q000737:chemistry* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001095:Arachidonic Acids; D016328:NF-kappa B; D010743:Phospholipids; C045533:eicosa-5,11,14-trienoic acid; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D020929:Mitogen-Activated Protein Kinase Kinases