| First Author | Portillo JA | Year | 2012 |
| Journal | Immunology | Volume | 135 |
| Issue | 2 | Pages | 140-50 |
| PubMed ID | 22044243 | Mgi Jnum | J:181390 |
| Mgi Id | MGI:5311263 | Doi | 10.1111/j.1365-2567.2011.03519.x |
| Citation | Portillo JA, et al. (2012) CD40 and tumour necrosis factor-alpha co-operate to up-regulate inducuble nitric oxide synthase expression in macrophages. Immunology 135(2):140-50 |
| abstractText | Regulation of inducible nitric oxide synthase (NOS2) expression is important given the role of this enzyme in inflammation, control of infections and immune regulation. In contrast to tumour necrosis factor-alpha (TNF-alpha) alone or CD40 stimulation alone, simultaneous stimulation of mouse macrophages through CD40 ligation and TNF-alpha led to up-regulation of NOS2 and nitric oxide production. This response was of functional relevance because CD40/TNF-alpha-stimulated macrophages acquired nitric oxide-dependent anti-Leishmania major activity. CD40 plus TNF-alpha up-regulated NOS2 independently of interferon-gamma, interferon-alpha/beta and interleukin-1. TNF receptor-associated factor 6 (TRAF6), an adapter protein downstream of CD40, appears to be required for NOS2 up-regulation because a CD40-TRAF6 blocking peptide inhibited up-regulation of NOS2 in CD40/TNF-alpha-stimulated macrophages. CCAAT/enhancer-binding protein-beta (C/EBPbeta), a transcription factor activated by TNF-alpha but not CD40, was required for NOS2 up-regulation because this enzyme was not up-regulated when C/EBPbeta(-/-) macrophages received CD40 plus TNF-alpha stimulation. These results indicate that CD40 and TNF-alpha co-operate to up-regulate NOS2, probably via the effect of TRAF6 and C/EBPbeta. |
