| First Author | Setoguchi K | Year | 2001 |
| Journal | J Clin Invest | Volume | 108 |
| Issue | 11 | Pages | 1667-75 |
| PubMed ID | 11733562 | Mgi Jnum | J:73140 |
| Mgi Id | MGI:2154617 | Doi | 10.1172/JCI13202 |
| Citation | Setoguchi K, et al. (2001) Peroxisome proliferator-activated receptor-gamma haploinsufficiency enhances B cell proliferative responses and exacerbates experimentally induced arthritis. J Clin Invest 108(11):1667-75 |
| abstractText | Peroxisome proliferator-activated receptor-gamma (PPARgamma) controls adipogenesis and glucose metabolism. It was reported recently that PPARgamma activation by its agonistic ligands modifies lymphocyte function. Since synthetic ligands are known to exert their effect via PPARgamma-dependent and -independent pathways, we examined the physiological role of PPARgamma in lymphocytes by using heterozygote mutant mice in which one allele of PPARgamma is deleted (PPARgamma(+/-)). In contrast to T cells, which did not exhibit a significant difference, B cells from PPARgamma(+/-) showed an enhanced proliferative response to stimulation by either lipopolysaccharide or cross-linking of antigen receptors. Dysregulation of the NF-kappaB pathway in B cells from PPARgamma(+/-) was indicated by spontaneous NF-kappaB activation, as well as increased IkappaBalpha phosphorylation and gel-shift activity following LPS stimulation. Mice primed with either ovalbumin or methylated BSA also showed enhanced antigen-specific immune response of both T and B cells, an immunological abnormality that exacerbated antigen-induced arthritis. These findings indicate that PPARgamma plays a critical role in the control of B cell response and imply a role in diseases in which B cell hyperreactivity is involved, such as arthritis and autoimmunity. |
