Sulfur mustard upregulates the expression of interleukin-8 in cultured human keratinocytes.
Although the morphological description of sulfur mustard (SM) injury is well characterised, little is known of the molecular mediators involved in cutaneous toxicity. Since infiltration by lymphocytes and PMNs represents one of the very first events observed in vivo upon exposure to SM, this study examined whether SM exposure can modify the expression by cultured human keratinocytes of interleukin-8, one of the most important chemoattractants for polymorphonuclear leukocytes (PMNs) in humans. Conditioned medium harvested from control keratinocyte cultures showed a gradual accumulation of this cytokine over time followed by a levelling off after 12 hours. Upon treatment with 10(-6) and 10(-5) M SM, no significant difference compared to the control 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 accumulation of the cytokine persisted up to 24 h after exposure. The expression of IL-8 mRNA was assessed semi-quantitatively (RT-PCR) at the same time points in control and SM-treated (10(-4) M) human keratinocytes. When compared to control cultures, a clear upregulation of IL-8 mRNA levels was observed 6 and 12 h after SM exposure, which is consistent with the secretion pattern of the protein. The present observation indicates that increased secretion of IL-8 by human keratinocytes represents an early event of the inflammatory reaction following SM which is coherent with the reported delay in the recruitment of lymphocytes and PMNs observed in vivo.
Lardot
C
C
Industrial Toxicology and Occupational Medicine Unit, Catholic University of Louvain, Brussels, Belgium.
Dubois
V
V
Lison
D
D
D000818:Animals; D002478:Cells, Cultured; D002619:Chemical Warfare Agents / Q000633:toxicity*; D002630:Chemotactic Factors / Q000096:biosynthesis; D006801:Humans; D007202:Indicators and Reagents; D007375:Interleukin-1 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis*; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D009151:Mustard Gas / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation
D002619:Chemical Warfare Agents; D002630:Chemotactic Factors; D007202:Indicators and Reagents; D007375:Interleukin-1; D016209:Interleukin-8; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D009151:Mustard Gas