Sulfur mustard upregulates the expression of interleukin-8 in cultured human keratinocytes

Although the morphological description of sulfur mustard (SM) injury is wel l characterised, little is known of the molecular mediators involved in cut aneous toxicity. Since infiltration by lymphocytes and PMNs represents one of the very first events observed in vivo upon exposure to SM, this study e xamined whether SM exposure can modify the expression by cultured human ker atinocytes of interleukin-8, one of the most important chemoattractants for polymorphonuclear leukocytes (PMNs) in humans. Conditioned medium harveste d from control keratinocyte cultures showed a gradual accumulation of this cytokine over time followed by a levelling off after 12 hours. Upon treatme nt with 10(-6) and 10(-5) M SM, no significant difference compared to the c ontrol situation was observed. After 6 h, a significantly higher amount of IL-8 was secreted by human keratinocytes treated with 10(-4) M SM and the a ccumulation of the cytokine persisted up to 24 h after exposure. The expres sion of IL-8 mRNA was assessed semi-quantitatively (RT-PCR) at the same tim e points in control and SM-treated (10(-4) M) human keratinocytes. When com pared to control cultures, a clear upregulation of IL-8 mRNA levels was obs erved 6 and 12 h after SM exposure, which is consistent with the secretion pattern of the protein. The present observation indicates that increased se cretion of IL-8 by human keratinocytes represents an early event of the inf lammatory reaction following SM which is coherent with the reported delay i n the recruitment of lymphocytes and PMNs observed in vivo. (C) 1999 Publis hed by Elsevier Science Ireland Ltd. All rights reserved.