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

Interleukin (IL)-19, a member of the IL-10 cytokine family, is involved in keratinocyte proliferation in psoriasis.

We investigated the role of IL-19 in the wound-healing process in vivo and in vitro.

Two full-thickness circular wounds (4mm 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 (400ng/mL), or IL-20 (400ng/mL) (n=6 in each group) twice daily and the percentage of wound healing was measured daily for 7days. 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.

In wounded mouse skin, IL-19 mRNA was upregulated at 12h, and KGF at 24h after the injury. Both increases in gene expression declined 72h 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.

IL-19 is important for cutaneous wound healing because it upregulates KGF expression.