Regulation of type V phospholipase A2 expression and function by proinflammatory stimuli.
Types IIA and V secretory phospholipase A2 (sPLA2) are structurally related to each other and their genes are tightly linked to the same chromosome locus. An emerging body of evidence suggests that sPLA2-IIA plays an augmentative role in long-term prostaglandin (PG) generation in cells activated by proinflammatory stimuli; however, the mechanism underlying the functional regulation of sPLA2-V remains largely unknown. Here we show that sPLA2-V is more widely expressed than sPLA2-IIA in the mouse, in which its expression is elevated by proinflammatory stimuli such as lipopolysaccharide. In contrast, proinflammatory stimuli induced sPLA2-IIA in marked preference to sPLA2-V in the rat. Cotransfection of sPLA2-V with cyclooxygenase (COX)-2, but not with COX-1, into human embryonic kidney 293 cells dramatically increased the interleukin-1-dependent PGE2 generation occurring over a 24 h of culture period. Rat mastocytoma RBL-2H3 cells overexpressing sPLA2-V exhibited increased IgE-dependent PGD2 generation and accelerated beta-hexosaminidase exocytosis. These results suggest that sPLA2-V acts as a regulator of inflammation-associated cellular responses. This possible compensation of sPLA2-V for sPLA2-IIA in many, if not all, tissues may also explain why some mouse strains with natural disruption of the sPLA2-IIA gene exhibit few abnormalities during their life-spans.
Sawada
H
H
Department of Health Chemistry, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Murakami
M
M
Enomoto
A
A
Shimbara
S
S
Kudo
I
I
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002460:Cell Line; D015232:Dinoprostone / Q000378:metabolism; D005089:Exocytosis; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology*; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007249:Inflammation; D007375:Interleukin-1 / Q000494:pharmacology; D007527:Isoenzymes; D007668:Kidney; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008407:Mast Cells / Q000201:enzymology; D012515:Mast-Cell Sarcoma; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010741:Phospholipases A / Q000096:biosynthesis / Q000235:genetics*; D054467:Phospholipases A2; D015230:Prostaglandin D2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000096:biosynthesis; D014162:Transfection; D014407:Tumor Cells, Cultured; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
D007375:Interleukin-1; D007527:Isoenzymes; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D006493:Heparin; D010741:Phospholipases A; D054467:Phospholipases A2; D001619:beta-N-Acetylhexosaminidases; D015232:Dinoprostone; D015230:Prostaglandin D2