| First Author | Linke A | Year | 2010 |
| Journal | J Invest Dermatol | Volume | 130 |
| Issue | 3 | Pages | 866-75 |
| PubMed ID | 19924141 | Mgi Jnum | J:159551 |
| Mgi Id | MGI:4443250 | Doi | 10.1038/jid.2009.345 |
| Citation | Linke A, et al. (2010) Epithelial overexpression of SOCS-3 in transgenic mice exacerbates wound inflammation in the presence of elevated TGF-beta1. J Invest Dermatol 130(3):866-75 |
| abstractText | The suppressor of cytokine signaling (SOCS)-3 has been shown to impair proliferation and migration of keratinocytes. To assess the functional dependency among wound inflammation, SOCS-3 induction in keratinocytes, and the outcome of healing, we generated a transgenic mouse that specifically overexpresses SOCS-3 in keratinocytes. Acute wound healing in transgenic mice was severely impaired. Keratinocyte-specific overexpression of SOCS-3 led to atrophied wound-margin epithelia and augmented the inflammatory response of wound keratinocytes by an increase in chemokine (MIP-2) and inflammatory enzyme (COX-2 and iNOS) expression. In addition, wound tissue of transgenic mice showed a prolonged persistence of neutrophils and macrophages. Remarkably, impaired wounds showed elevated levels of transforming growth factor (TGF)-beta1, which appeared to interfere with healing, as its neutralization markedly improved wound closure in transgenic mice. Interestingly, administration of a TGF-beta-neutralizing antibody increased wound inflammation in nontransgenic mice but not in transgenic littermates. This study suggests that SOCS-3-driven disturbances in wound keratinocytes are sufficient to induce inflamed wound conditions that resemble characteristics of chronic wounds in mice. |
