Epidermis as a Secretory Tissue

Abstract

C ompelling evidence has accumulated during recent years to support a theory that epidermal keratinocytes synthesize and deliver to the extracellular space a wide variety of gene products. Each of these cellular products has unique physical-chemical properties resulting from its biochemical structure that define its a) relative solubility and ability to diffuse under physiologic conditions; b) probability of spontaneous assembly into higher order structures; c) specific affinity for ligands or cell surface receptors of target cells; and/or d) specific catalytic activity. Depending on the concentration of the gene product relative to its receptor or substrate, it may regulate stimulation or inhibition of cellular function. Gene products of keratinocytes known to be delivered to the extracellular space include cytokines, enzymes, and adhesion molecules, which together constitute the majority of the regulatory environment of epidermal tissue. Uninjured skin maintains a steady-state equilibrium of relatively slow metabolism of gene products. By comparison, injury or disease initiates expression by keratinocytes of several potent inflammatory mediators including interleukins (ILs)-l, -3, -6, -7, -8, -10, granulocyte colony stimulating factor (G-CSF) , granulocyte-monocyte stimulating factor (GM-CSF), and arachidonic acid metabolites that are associated with acute phase dermatitis and systemic response [1,2] . After whole body irradiation with ultraviolet (UV) light, significantly elevated circulating levels of ILs-1 and -6 correlate with induction of fever in humans [3,4]. Keratinocytes in culture also produce and release parathyroid hor1110ne-related protein (PTHrP), which is believed to participate in regulation of epidermal differentiation [5]. Collagenases and tissue plasminogen activator (TPA) are synthesized and secreted by cultured keratinocytes [6,7], and transforming growth factor beta 1 (TGF-fi1) has been shown to stimulate collagenase expression in keratinocytes [8]. Increased expression of intercellular adhesion molecule-l (ICAM-1) by keratinocytes after injury has been suggested to facilitate T -lymphocyte infiltration in contact dermatitis, perhaps by establishment of a gradient toward the site of injury [9]. Several basement membrane components are secreted by keratinocytes, including the hemidesmosome protein, kalinin [10). Taichman and colleagues have demonstrated circu lating levels of human apolipoprotein E (Apo E) derived from epidermal keratinocytes in vitro l11, 12], and in serum after grafting of cultured epidermal keratinocyte~ to .athymic mice [13]. From these kinds of examples, it fo llows llltUltlVely that epidermis may secrete other gene products that may regulate extracellular or systemic responses .