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.