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Lack of Interferon-γ Production Despite the Presence of Interleukin-18 During Cutaneous Wound Healing

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Abstract

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-γ (IFN-γ) production at the wound site.

Materials and Methods

Expression of IFN-γ 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-γ 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-γ. 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-γ in response to IL-18. Furthermore, we provide evidence that the presence of transforming growth factor-β1 (TGF-β1) at the wound site might reflect a counterregulatory mechanism in IL-18-induced IFN-γ production, as TGF-β1 strongly suppressed IL-18/phytohaemagglutinin (PHA)-induced IFN-γ 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-γ in vivo, and IL-18 must serve additional roles rather than inducing IFN-γ during the healing process.

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Acknowledgments

We thank Nicole Kolb for her excellent technical assistance. We gratefully acknowledge Dr. Martin Kock for his help regarding the animal experiments. This work was supported by a grant of the Adolf Messer-Stiftung.

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Authors and Affiliations

  1. pharmazentrum Frankfurt, Klinikum der Johann Wolfgang Goethe-Universität, Theodor-Stern-Kai 7, D-60590, Frankfurt am Main, Germany

    Heiko Kämpfer, Jens Paulukat, Heiko Mühl, Christian Wetzler, Josef Pfeilschifter & Stefan Frank

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  1. Heiko Kämpfer
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  2. Jens Paulukat
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Correspondence to Stefan Frank.

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Kämpfer, H., Paulukat, J., Mühl, H. et al. Lack of Interferon-γ Production Despite the Presence of Interleukin-18 During Cutaneous Wound Healing. Mol Med 6, 1016–1027 (2000). https://doi.org/10.1007/BF03402053

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