Lack of interferon-γ production despite the presence of interleukin-18 during cutaneous wound healing

被引:38
|
作者
Kämpfer, H [1 ]
Paulukat, J [1 ]
Mühl, H [1 ]
Wetzler, C [1 ]
Pfeilschifter, J [1 ]
Frank, S [1 ]
机构
[1] Univ Frankfurt Klinikum, Pharmazentrum Frankfurt, D-60590 Frankfurt, Germany
关键词
D O I
10.1007/BF03402053
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: Recently, we have reported a rapid and strong induction of interleukin-18 (IL-18) upon cutaneous injury in mice. In this paper, we investigated a possible role of IL-18 in triggering interferon-gamma (IFN-gamma) production at the wound site. Materials and Methods: Expression of IFN-gamma during cutaneous wound healing was analyzed by RNase protection assay, Western blot, ELISA, and immunohistochemical techniques in a murine model of excisional skin repair. Results: We could not detect any IFN-gamma mRNA and protein expression during normal skin repair. Additionally, impaired healing in the genetically diabetic db/db mouse, which was used as a model for a prolonged inflammatory phase of repair, was characterized by largely elevated levels of IL-18 during the late phase of repair and an absence of IFN-gamma. Western blot analysis for T-cell- and monocyte/macrophage-specific marker proteins (CD4, F4/80) clearly revealed the presence of these subsets of leukocytic cells at the wound site, that are known to produce IFN-gamma in response to IL-18. Furthermore, we provide evidence that the presence of transforming growth factor-beta1 (TGF-beta1) at the wound site might reflect a counterregulatory mechanism in IL-18-induced IFN-gamma production, as TGF-P I strongly suppressed IL-18/phytohaemagglutinin (PHA)-induced IFN-gamma production by peripheral blood mononuclear cells (PBMC) in vitro. Conclusions: Normal tissue regeneration processes after cutaneous injury were not dependent on the presence of IFN-gamma in vivo, and IL-18 must serve additional roles rather than inducing IFN-gamma during the healing process.
引用
收藏
页码:1016 / 1027
页数:12
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