Interleukin (IL)-19 promoted skin wound healing by increasing fibroblast keratinocyte growth factor expression

Background: Interleukin (IL)-19, a member of the IL-10 cytokine family, is involved in keratinocyte proliferation in psoriasis. Objectives: We investigated the role of IL-19 in the wound-healing process in vivo and in vitro. Methods: Two full-thickness circular wounds (4. mm in diameter) were punched into the skin of BALB/C mice. IL-19 and keratinocyte growth factor (KGF) mRNA in wounded skin were determined using real-time PCR. The wounds were treated with PBS, vehicle, IL-19 (400. ng/mL), or IL-20 (400. ng/mL) (. n=. 6 in each group) twice daily and the percentage of wound healing was measured daily for 7. days. In vitro, human skin fibroblast CCD966-SK cells and keratinocyte HaCaT cells were treated with IL-19 or KGF. Cell proliferation and migration were determined using bromodeoxyuridine (BrdU) and transwell assays, respectively. The expression of IL-19 and KGF mRNA was also analyzed. Results: In wounded mouse skin, IL-19 mRNA was upregulated at 12. h, and KGF at 24. h after the injury. Both increases in gene expression declined 72. h after the skin had been wounded. The percentage of wound healing in IL-19-treated mice was higher than in control mice. In vitro, IL-19 upregulated KGF expression in the CCD966-SK cells; IL-19 was upregulated in KGF-treated HaCaT cells. KGF but not IL-19 promoted HaCaT cell proliferation. However, IL-19 significantly increased the migration of HaCaT cells. HaCaT cells treated with the cultured supernatants of IL-19-stimulated CCD966-SK cells showed significantly more proliferation than in controls. Conclusions: IL-19 is important for cutaneous wound healing because it upregulates KGF expression.