| First Author | Weaver BK | Year | 2007 |
| Journal | Mol Cell Biol | Volume | 27 |
| Issue | 13 | Pages | 4603-16 |
| PubMed ID | 17485448 | Mgi Jnum | J:122758 |
| Mgi Id | MGI:3715406 | Doi | 10.1128/MCB.00223-07 |
| Citation | Weaver BK, et al. (2007) ABIN-3: a molecular basis for species divergence in interleukin-10-induced anti-inflammatory actions. Mol Cell Biol 27(13):4603-16 |
| abstractText | Whereas interleukin-10 (IL-10) is an anti-inflammatory cytokine known to regulate macrophage activation, its full mechanism of action remains incompletely defined. In a screen to identify novel IL-10-induced genes, we cloned the mouse ortholog of human ABIN-3 (also termed LIND). ABIN-3 expression was induced selectively by IL-10 in both mouse and human mononuclear phagocytes coordinately undergoing proinflammatory responses. In contrast to the previously characterized ABINs, mouse ABIN-3 was incapable of inhibiting NF-kappaB activation by proinflammatory stimuli. Generation and analysis of ABIN-3-null mice demonstrated that ABIN-3 is unnecessary for the anti-inflammatory effects of IL-10 as well as for proper negative regulation of NF-kappaB. Conversely, human ABIN-3 was capable of inhibiting NF-kappaB activation in response to signaling from Toll-like receptor, IL-1, and tumor necrosis factor. Enforced expression of human ABIN-3 in human monocytic cells suppressed the cytoplasmic degradation of IkappaBalpha, the activation of NF-kappaB, and the induction of proinflammatory genes. Comparative sequence analyses revealed that mouse ABIN-3 lacks a complete ABIN homology domain, which was required for the functional activity of human ABIN-3. ABIN-3 is, thus, an IL-10-induced gene product capable of attenuating NF-kappaB in human macrophages yet is inoperative in mice and represents a basis for species-specific differences in IL-10 actions. |
