Protective role for cytosolic phospholipase A2alpha in autoimmune diabetes of mice.
Cytosolic phospholipase A(2)alpha (cPLA(2)alpha) plays an important role in arachidonate pathway. To investigate the contribution of cPLA(2)alpha to autoimmune diabetes, we established non-obese diabetic (NOD) mouse, an excellent model for human type 1 diabetes, deficient in cPLA(2)alpha. These mice showed severe insulitis and a higher incidence of diabetes. In their macrophages, decreased prostaglandin E(2) (PGE(2)) induced by cPLA(2)alpha deficiency, and the increase in production of tumor necrosis factor (TNF)-alpha were observed. These results suggested that cPLA(2)alpha plays a protective role in progression of insulitis and development of autoimmune diabetes by suppression of TNF-alpha production from macrophages.
Division of Stem Cell Regulation Research, G6, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan. oikawa@sc.itc.keio.ac.jp
Y
Y
Oikawa
E
E
Yamato
F
F
Tashiro
M
M
Yamamoto
N
N
Uozumi
A
A
Shimada
T
T
Shimizu
J
J
Miyazaki
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology*; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D054513:Group IV Phospholipases A2; D006801:Humans; D007328:Insulin / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D018895:Microsatellite Repeats; D010741:Phospholipases A / Q000737:chemistry / Q000502:physiology*; D016133:Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007328:Insulin; D014409:Tumor Necrosis Factor-alpha; D016718:Arachidonic Acid; D010741:Phospholipases A; D054513:Group IV Phospholipases A2