| First Author | Kojima F | Year | 2008 |
| Journal | J Immunol | Volume | 180 |
| Issue | 12 | Pages | 8361-8 |
| PubMed ID | 18523303 | Mgi Jnum | J:137134 |
| Mgi Id | MGI:3798103 | Doi | 10.4049/jimmunol.180.12.8361 |
| Citation | Kojima F, et al. (2008) Defective generation of a humoral immune response is associated with a reduced incidence and severity of collagen-induced arthritis in microsomal prostaglandin E synthase-1 null mice. J Immunol 180(12):8361-8 |
| abstractText | Microsomal PGE synthase-1 (mPGES-1) is an inducible enzyme that acts downstream of cyclooxygenase and specifically catalyzes the conversion of PGH(2) to PGE(2). The present study demonstrates the effect of genetic deletion of mPGES-1 on the developing immunologic responses and its impact on the clinical model of bovine collagen-induced arthritis. mPGES-1 null and heterozygous mice exhibited decreased incidence and severity of arthritis compared with wild-type mice in a gene dose-dependent manner. Histopathological examination revealed significant reduction in lining hyperplasia and tissue destruction in mPGES-1 null mice compared with their wild-type littermates. mPGES-1 deficient mice also exhibited attenuation of mechanical nociception in a gene dose-dependent manner. In addition, mPGES-1 null and heterozygous mice showed a marked reduction of serum IgG against type II collagen, including subclasses IgG1, IgG2a, IgG2b, IgG2c, and IgG3, compared with wild-type mice, which correlated with the reduction in observed inflammatory features. These results demonstrate for the first time that deficiency of mPGES-1 inhibits the development of collagen-induced arthritis, at least in part, by blocking the development of a humoral immune response against type II collagen. Pharmacologic inhibition of mPGES-1 may therefore impact both the inflammation and the autoimmunity associated with human diseases such as rheumatoid arthritis. |
