Epithelial overexpression of SOCS-3 in transgenic mice exacerbates wound inflammation in the presence of elevated TGF-beta1.

Abstract

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.

• Authors: Andreas Linke, Itamar Goren, Michael R Bösl, Josef Pfeilschifter, Stefan Frank
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 130 Issue 3 Pg. 866-75 (Mar 2010) ISSN: 1523-1747 [Electronic] United States
• PMID: 19924141 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies
• Chemokine CXCL2
• Cxcl2 protein, mouse
• Socs3 protein, mouse
• Suppressor of Cytokine Signaling 3 Protein
• Suppressor of Cytokine Signaling Proteins
• Transforming Growth Factor beta1

Topics

• Animals
• Animals, Newborn
• Antibodies (pharmacology)
• Cells, Cultured
• Chemokine CXCL2 (genetics, metabolism)
• Chronic Disease
• Dermatitis (immunology, pathology, physiopathology)
• Gene Expression (physiology)
• Keratinocytes (cytology, physiology)
• Macrophages (pathology)
• Mice
• Mice, Transgenic
• Neutrophils (pathology)
• Skin (injuries, pathology)
• Suppressor of Cytokine Signaling 3 Protein
• Suppressor of Cytokine Signaling Proteins (genetics, metabolism)
• Transforming Growth Factor beta1 (genetics, immunology, metabolism)
• Wound Healing (physiology)