Strain differences regarding susceptibility to ursolic acid-induced interleukin-1beta release in murine macrophages.
Interleukin (IL)-1beta is a proinflammatory cytokine responsible for the onset of a broad range of diseases, such as inflammatory bowel disease and rheumatoid arthritis. We have recently found that aggregated ursolic acid (UA), a triterpene carboxylic acid, is recognized by CD36 for generating reactive oxygen species (ROS) via NADPH oxidase (NOX) activation, thereby releasing IL-1beta protein from murine peritoneal macrophages (pMphi) in female ICR mice. In the present study, we investigated the ability of UA for inducing IL-1beta production in pMphi from 4 different strains of female mice (C57BL/6J, C3H/He, DDY, and ICR), as well as an established macrophage line (RAW264.7 cells). The levels of IL-1beta released from UA-treated pMphi of C57BL/6J and DDY mice were significantly lower than from those of ICR mice, whereas IL-1beta was not released from the pMphi of C3H/He mice or RAW264.7 cells. Of paramount importance, CD36 as well as the NOX components gp91phox and p47phox (C3H/He mice) and gp91phox (RAW264.7 cells) were scarcely detected. In addition, the different susceptibilities to UA-induced IL-1beta release were suggested to be correlated with the amount of superoxide anion (O2-) generated from the 5 different types of Mphi. Notably, intracellular, but not extracellular, O2- generation was indicated to play a major role in UA-induced IL-1beta release. Together, our results indicate that the UA-induced IL-1beta release was strain-dependent, and the expression status of CD36 and gp91phox is strongly associated with inducibility.
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan.
Yasutaka
Y
Ikeda
Akira
A
Murakami
Hajime
H
Ohigashi
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D005260:Female; D053583:Interleukin-1beta / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D051379:Mice; D008813:Mice, Inbred ICR; D008815:Mice, Inbred Strains; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D009861:Onium Compounds / Q000494:pharmacology; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051116:Receptors, Scavenger / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*; D000097245:Ursolic Acid
D053583:Interleukin-1beta; D019255:NADPH Oxidases; D009861:Onium Compounds; D021122:Protein Subunits; D012333:RNA, Messenger; D051116:Receptors, Scavenger; D013482:Superoxide Dismutase; D013481:Superoxides; D051197:Toll-Like Receptor 4; D014315:Triterpenes; D000097245:Ursolic Acid; C493487:Tlr4 protein, mouse; C007517:diphenyleneiodonium