HUMAN KERATINOCYTES ARE A SOURCE FOR TUMOR-NECROSIS-FACTOR-ALPHA - EVIDENCE FOR SYNTHESIS AND RELEASE UPON STIMULATION WITH ENDOTOXIN OR ULTRAVIOLET-LIGHT

Tumor necrosis factor α (TNF-α), in addition to being cytotoxic for certain tumor cells, has turned out as a multifunctional cytokine that is involved in the regulation of immunity and inflammation. Since human keratinocytes have been demonstrated to be a potent source of various cytokines, it was investigated whether epidermal cells synthesize and release TNF-m Supernatants derived from normal human keratinocytes (HNK) and human epidermoid carcinoma cell lines (KB, A431) were tested both in a TNF-α-specific ELISA and a bioassay. In supernatants of untreated epidermal cells, no or minimal TNF-α activity was found, while after stimulation with lipopolysaccharide (LPS) or ultraviolet (UV) light, significant amounts were detected. Western blot analysis using an antibody directed against human TNF-α revealed a molecular mass of 17 kD for keratinocyte-derived TNF-α. These biological and biochemical data were also confirmed by Northern blot analysis revealing mRNA specific for TNF-α in LPS- or ultraviolet B (UVB)- treatedHNK and KB cells. In addition, increased TNF-α levels were detected in the serum obtained from human volunteers 12 and 24 h after a single total body UVB exposure, which caused a severe sunburn reaction. These findings indicate that keratinocytes upon stimulation are able to synthesize and release TNF-α, which may gain access to the circulation. Thus, TNF-α in concert with other epidermal cell-derived cytokines may mediate local and systemic inflammatory reactions during host defense against injurious events caused by microbial agents or UV irradiation. © 1990, Rockefeller University Press., All rights reserved.