| First Author | Korhonen R | Year | 2012 |
| Journal | Mol Immunol | Volume | 51 |
| Issue | 2 | Pages | 219-26 |
| PubMed ID | 22464096 | Mgi Jnum | J:184869 |
| Mgi Id | MGI:5426488 | Doi | 10.1016/j.molimm.2012.03.019 |
| Citation | Korhonen R, et al. (2012) The expression of interleukin-12 is increased by MAP kinase phosphatase-1 through a mechanism related to interferon regulatory factor 1. Mol Immunol 51(2):219-26 |
| abstractText | Mitogen-activated protein kinase phosphatase-1 (MKP-1) is a nuclear tyrosine/threonine phosphatase that inhibits p38 mitogen-activated protein kinase (MAPK) activity. We and others have shown that MKP-1 deficiency leads to excessive activation of innate immunity and inflammatory gene expression. Surprisingly, the present study shows that MKP-1 is a positive regulator of IL-12 expression in macrophages suggesting a stimulatory effect on Th1 type immune response. In the present study, we found that LPS-induced expression of IL-12p40 was lower in primary mouse peritoneal macrophages (PMs) and bone marrow-derived macrophages from MKP-1 deficient mice than in cells from wild-type mice whereas TNF expression was enhanced as expected. Correspondingly, the inhibition of p38 MAPK by pharmacologic inhibitors BIRB 796 and SB 202190 enhanced LPS-induced IL-12p40 production. Silencing of interferon regulatory factor 1 (IRF1) by siRNA inhibited the expression of IL-12p40 in J774 macrophages, showing that IRF1 is an important factor regulating IL-12p40 expression. BIRB 796 enhanced LPS-induced expression of IRF1 in J774 macrophages and in PMs from wild-type mice, and IRF1 expression was reduced in PMs from MKP-1 deficient mice. In conclusions, our results show that MKP-1 increases and p38 MAPK decreases the expression of IL-12 by enhancing the expression of IRF1. MKP-1, through regulation of IRF1 and IL-12, therefore may be an important factor supporting the development of Th1 type of immune response and anti-microbial defense. |
