Regulation of 1-alpha, 25-dihydroxyvitamin D3 on interleukin-6 and interleukin-8 induced by sulfur mustard (HD) on human skin cells.
The regulatory effects of the active form of vitamin D, 1-alpha, 25-dihydroxyvitamin D3 (1-alpha, 25 (OH)2D3) were assessed on the cytokine and chemokine secretion induced by sulfur mustard on human skin fibroblasts and human epidermal keratinocytes. Stimulation of human skin fibroblasts with sulfur mustard (10(-4) M for 24 hr at 37 degrees ) resulted in approximately a 5 times increase in the secretion of interleukin-6 and over a 10 times increase for interleukin-8, which was inhibited by 1-alpha, 25 (OH)2D3, at <or=10(-9) M. 1-alpha, 25 (OH)2D3 also suppressed interleukin-8 secretion by 5 times and interleukin-6 by 4 times on sulfur mustard-stimulated human epidermal keratinocytes at concentrations <or= 10(-9) M. The effect of 1-alpha, 25 (OH)2D3 was dose-dependent for the suppression of interleukin-6 and interleukin-8 induced by sulfur mustard on human skin fibroblasts/human epidermal keratinocytes, apparent at nanomolar concentrations. Our results indicate that the suppression of these inflammatory mediators by 1-alpha, 25 (OH)2D3 is dependent on the source of the primary cultures, cell densities, and kinetics of pretreatments. In contrast to the inhibition of cytokine/chemokine production, cell proliferation was enhanced by almost 1.7 times on treated human epidermal keratinocytes with 1-alpha, 25 (OH)2D3 (1 x 10(-9) M) after sulfur mustard-stimulation (10(-4) M for 24 hr at 37 degrees C). The observed enhancement diversified based on cell density, and kinetics of pretreatment with a maximal synergism (s) observed at 1 x 10(-9) M. Photomicrographs show typical signs of cellular degeneration caused by sulfur mustard such as chromatin condensation. The observed cellular degeneration was lessened when human epidermal keratinocytes were treated with 1-alpha, 25 (OH)2D3 (2 x 10(-9) M). 1-alpha, 25(OH)2D3 could be an alternative treatment for cutaneous inflammation disorders caused by sulfur mustard because we have demonstrated its ability to suppress inflammatory mediators and enhanced cell proliferation in human skin cells stimulated with sulfur mustard.
Arroyo
Carmen M
CM
Drug Assessment Division, Comparative Medicine, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5400, USA. carmen.arroyo@amedd.army.mil
Kan
Robert K
RK
Burman
Damon L
DL
Kahler
David W
DW
Nelson
Marian R
MR
Corun
Charlene M
CM
Guzman
Juanita J
JJ
Broomfield
Clarence A
CA
D000279:Administration, Cutaneous; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002117:Calcitriol / Q000008:administration & dosage / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002619:Chemical Warfare Agents / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006651:Histocytochemistry; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D009151:Mustard Gas / Q000633:toxicity*; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D002619:Chemical Warfare Agents; D015850:Interleukin-6; D016209:Interleukin-8; D002117:Calcitriol; D009151:Mustard Gas