The activated keratinocyte: a model for inducible cytokine production by non-bone marrow-derived cells in cutaneous inflammatory and immune responses

Abstract

Keratinocytes, fibroblasts, endothelial cells, and other sessile cells resident to human skin can be induced in vitro to synthesize and secrete cytokine molecules. Cytokines are small protein molecules produced upon injury or cellular activation which influence immune and inflammatory events; as such, they have been best understood previously as products of leukocytes. The appreciation that cultured non-bone marrow-derived cells from skin could produce cytokines capable of initiating an inflammatory response or facilitating an immune response has led to speculation that cells resident to skin may be less passive participants in such phenomena than previously thought. Using as a model the cultured keratinocyte, which produces both interleukin-1 alpha and beta and an interleukin-1 receptor, models of autocrine and paracrine activation of this cell have been constructed. Such "activated keratinocytes," or by analogy other activated resident skin cells, produce a spectrum of cytokines in vitro which could potentially influence leukocyte adhesion to endothelium, direction migration of leukocytes towards the activated cell (presumably an inflammatory nidus), and activation of leukocyte functions in situ. The putative role of regulation of cytokine and cytokine-receptor regulation in mediating the activation of such cells (and thus, presumably, local inflammation) is discussed. An important aspect of this hypothetical model is that in the absence of activation (which characterizes normal uninflamed skin), cytokine production and its consequences do not occur. The conclusion reached is that based on in vitro data it is plausible to guess that local inflammatory or immune responses can be both initiated and facilitated by locally produced cytokines.