| First Author | Yamashita J | Year | 2013 |
| Journal | J Immunol | Volume | 191 |
| Issue | 2 | Pages | 949-60 |
| PubMed ID | 23772025 | Mgi Jnum | J:204816 |
| Mgi Id | MGI:5543521 | Doi | 10.4049/jimmunol.1201828 |
| Citation | Yamashita J, et al. (2013) Paraoxonase-1 suppresses experimental colitis via the inhibition of IFN-gamma production from CD4 T cells. J Immunol 191(2):949-60 |
| abstractText | Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract, where excessive Th1 cell responses are observed. We performed experiments to identify immunologically bioactive proteins in human plasma and found that paraoxonase (PON)-1, which has esterase activity and is associated with high-density lipoproteins, inhibited the IFN-gamma production by both murine and human differentiating Th1 cells. Trinitrobenzene sulfonic acid-induced colitis was attenuated by the administration of PON-1. The beneficial effects of PON-1 were associated with a reduced ratio of IFN-gamma-producing CD4 T cells in the mesenteric lymph nodes and decreased production of T cell-related cytokines in the colon. PON-1 inhibited the TCR-induced activation of ERK-MAPK signaling and the nuclear translocation of NF-kappaB in CD4 T cells. Interestingly, an excessive CD4 T cell response was observed in PON-1-deficient mice under physiological and pathological conditions. Additionally, the efficacy of PON-1 or G3C9-C284A (G3C9), which shows a higher esterase activity than PON-1, on colitis was similar to that of an anti-TNF-alpha mAb, which is a clinically used CD treatment. Moreover, G3C9 more effectively suppressed CD4(+)CD45RB(high) cell transfer-induced chronic colitis in mice than did PON-1, and the efficacy of G3C9 against the colitis was similar to that of the anti-TNF-alpha mAb. Therefore, PON-1 (or G3C9) administration may be clinically beneficial for CD patients. |
