LAUSR

The mitochondrial Ca2+-independent phospholipase A2γ (iPLA2γ) plays an antioxidant role in various tissues.1 iPLA2γ is redox-dependent, releasing free fatty acids as substrates for mitochondrial uncoupling protein 2 and possibly other SLC25 family carriers, resulting in the attenuation of mitochondrial superoxide formation.1 We tested the hypothesis that iPLA2γ participates in cellular antioxidant and anti-inflammatory protection in vivo. We found that steady-state serum levels of the pro-inflammatory cytokine interleukin-6 (IL-6) and of protein carbonylation were higher in iPLA2γ-KO and UCP2-KO mice compared to wild type (wt) controls. The wt IL-6 serum levels were also elevated to the levels in both types of KO mice upon administration of iPLA2γ-selective inhibitor r -BEL. The injection of the endotoxin lipopolysaccharide also resulted in a marked IL-6 increase in iPLA2γ-KO mice compared to the wt controls. These results show that redox upregulation of cytokine expression is prevented by the antioxidant and anti-inflammatory synergy of iPLA2γ-KO and UCP2, which ceases in the respective KO mice or upon r -BEL inhibition of iPLA2γ.