Growth-regulated peptide-alpha (GRO-alpha) production by oral keratinocytes: a comparison with skin keratinocytes

Growth regulated peptide (GRO-alpha) is chemotactic for neutrophils. It also stimulates keratinocyte proliferation and migration, and angiogenesis in cutaneous wound healing. We compared GRO-alpha production by normal human skin and oral keratinocytes, and the effects of cytokine stimulation. Resting keratinocytes produced little, if any, GRO-alpha. TNF-alpha induced a large increase in GRO-alpha mRNA and protein production in both cell types (P<0.001). However, the response of oral keratinocytes was significantly higher (P<0.01). Oral, but not skin, keratinocytes also produced significant amounts of GRO-alpha in response to IL-1 alpha (P<0.005) and IL-4 (P<0.01) stimulation. Indeed, there was an additive effect on GRO-alpha production when oral keratinocytes were stimulated with combinations of TNF-alpha and IL-1 alpha or TNF-alpha and IL-4. Neither cell type responded to interferon gamma. Keratinocyte GRO-alpha production may help selectively recruit neutrophils in mucocutaneous inflammatory diseases, and differences in production by skin and oral keratinocyte could explain the different presentation of these diseases at the two sites. The increased GRO-alpha responsiveness of oral keratinocytes may also help explain the excellent wound healing properties of oral mucosa.