| First Author | Reis J | Year | 2011 |
| Journal | Cell Biochem Biophys | Volume | 60 |
| Issue | 1-2 | Pages | 119-26 |
| PubMed ID | 21455681 | Mgi Jnum | J:175955 |
| Mgi Id | MGI:5287968 | Doi | 10.1007/s12013-011-9183-7 |
| Citation | Reis J, et al. (2011) The immunoproteasomes regulate LPS-induced TRIF/TRAM signaling pathway in murine macrophages. Cell Biochem Biophys 60(1-2):119-26 |
| abstractText | We have proposed the novel concept that the macrophage ubiquitin-proteasome pathway functions as a key regulator of Lipopolysaccharide (LPS)-induced inflammation signaling. These findings suggest that proteasome-associated protease subunits X, Y, and Z are replaced by LMP subunits after LPS treatment of RAW 264.7 cells. The objective here was to determine the contribution of selective LMP proteasomal subunits to LPS-induced nitric oxide (NO) and TNF-alpha production in primary murine macrophages. Accordingly, thioglycollate-elicited macrophages from LMP7, LMP2, LMP10 (MECL-1), and LMP7/MECL-1 double knockout mice were stimulated in vitro with LPS, and were found to generate markedly reduced NO levels compared to wild-type (WT) mice, whereas TNF-alpha levels responses were essentially unaltered relative to wild-type responses. The recent studies suggest that the TRIF/TRAM pathway is defective in LMP knockouts which may explain why iNOS/NO are not robustly induced in LPS-treated macrophages from knockouts. Treating these macrophages with IFN-gamma and LPS, however, reverses this defect, leading to robust NO induction. TNF-alpha is induced by LPS in the LMP knockout macrophages because IkappaB and IRAK are degraded normally via the MyD88 pathway. Collectively, these findings strongly support the concept that LMP7/MECL-1 proteasomes subunits actively function to regulate LPS-induced NO production by affecting the TRIF/TRAM pathway. |
