The essential involvement of cross-talk between IFN-gamma and TGF-beta in the skin wound-healing process.

Abstract

Several lines of in vitro evidence suggest the potential role of IFN-gamma in angiogenesis and collagen deposition, two crucial steps in the wound healing process. In this report, we examined the role of IFN-gamma in the skin wound healing process utilizing WT and IFN-gamma KO mice. In WT mice, excisional wounding induced IFN-gamma mRNA and protein expression by infiltrating macrophages and T cells, with a concomitant enhancement of IL-12 and IL-18 gene expression. Compared with WT mice, IFN-gamma KO mice exhibited an accelerated wound healing as evidenced by rapid wound closure and granulation tissue formation. Moreover, IFN-gamma KO mice exhibited enhanced angiogenesis with augmented vascular endothelial growth factor mRNA expression in wound sites, compared with WT mice, despite a reduction in the infiltrating neutrophils, macrophages, and T cells. IFN-gamma KO mice also exhibited accelerated collagen deposition with enhanced production of TGF-beta1 protein in wound sites, compared with WT mice. Furthermore, the absence of IFN-gamma augmented the TGF-beta1-mediated signaling pathway, as evidenced by increases in the levels of total and phosphorylated Smad2 and a reciprocal decrease in the levels of Smad7. These results demonstrate that there is crosstalk between the IFN-gamma/Stat1 and TGF-beta1/Smad signaling pathways in the wound healing process.

• Authors: Yuko Ishida, Toshikazu Kondo, Tatsunori Takayasu, Yoichiro Iwakura, Naofumi Mukaida
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 172 Issue 3 Pg. 1848-55 (Feb 01 2004) ISSN: 0022-1767 [Print] United States
• PMID: 14734769 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-18
• Transforming Growth Factor beta
• Vascular Endothelial Growth Factor A
• Interleukin-12
• Interferon-gamma

Topics

• Animals
• Cell Movement (genetics, immunology)
• Gene Expression Regulation (immunology)
• Granulation Tissue (immunology, physiopathology)
• Interferon-gamma (biosynthesis, deficiency, physiology)
• Interleukin-12 (biosynthesis)
• Interleukin-18 (biosynthesis)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Knockout
• Mice, SCID
• Neovascularization, Physiologic (immunology)
• Neutrophil Infiltration (genetics, immunology)
• Signal Transduction (genetics, immunology)
• Skin (immunology, metabolism, pathology)
• Transforming Growth Factor beta (physiology)
• Vascular Endothelial Growth Factor A (biosynthesis, genetics)
• Wound Healing (genetics, immunology)