| First Author | Tamiya H | Year | 2014 |
| Journal | J Immunol | Volume | 192 |
| Issue | 8 | Pages | 3793-804 |
| PubMed ID | 24634492 | Mgi Jnum | J:210010 |
| Mgi Id | MGI:5569229 | Doi | 10.4049/jimmunol.1302308 |
| Citation | Tamiya H, et al. (2014) IFN-gamma or IFN-alpha ameliorates chronic proliferative dermatitis by inducing expression of linear ubiquitin chain assembly complex. J Immunol 192(8):3793-804 |
| abstractText | The linear ubiquitin chain assembly complex (LUBAC) ubiquitin ligase complex, composed of HOIL-1L-interacting protein (HOIP), heme-oxidized IRP2 ubiquitin ligase-1L (HOIL-1L), and SHANK-associated RH domain protein, specifically generates linear polyubiquitin chains and is involved in NF-kappaB activation. Lack of SHANK-associated RH domain protein, which drastically reduces the amount of HOIP and HOIL-1L, causes chronic proliferative dermatitis (cpdm) in mice. Impaired NF-kappaB activation and augmented apoptosis have been implicated in the pathogenesis of cpdm in mice. In this study, we found that IFN-gamma increased the amount of LUBAC by inducing HOIP and HOIL-1L mRNA transcription and enhanced the signal-induced NF-kappaB activation in embryonic fibroblasts, keratinocytes, and bone marrow-derived macrophages from wild-type and/or cpdm mice; however, IFN-gamma failed to augment NF-kappaB activation in mouse embryonic fibroblasts lacking linear polyubiquitination activity of LUBAC. Moreover, s.c. injection of IFN-gamma for 3 wk into the skin of cpdm mice increased the amount of HOIP, suppressed apoptosis, and ameliorated the dermatitis. Inhibition of keratinocyte apoptosis by IFN-gamma injection suppressed neutrophil, macrophage, and mast cell infiltration and the amount of TNF-alpha in the skin of cpdm mice. Similarly, IFN-alpha also enhanced the amount of HOIP as well as NF-kappaB activation, inhibited apoptosis, and ameliorated cpdm dermatitis. These results indicate that the IFNs enhance NF-kappaB activation and ameliorate cpdm dermatitis by augmenting expression of HOIP and HOIL-1L and linear polyubiquitination activity of LUBAC. |
