Artificial human skin: cytokine, prostaglandin, Hsp70 and histological responses to heat exposure.
Artificial human skin, Skin2 (keratinocytes and fibroblasts) and EpiDerm (keratinocytes), was used to determine heat-induced release/accumulation of mediators of injury and repair. Skin2 was exposed to 37 or 41-45 degrees C for 90 min, followed by 37 degrees C for 22.5 h. Media were analyzed for interleukin-1alpha (IL-1alpha), prostaglandin-E2 (PGE2), thromboxane-B2 (TxB2) and nuclear matrix apparatus protein (NMAP, viability). Specimens were taken for microscopy. Media and lysates from Skin2 and EpiDerm (37 and 45 degrees C) were analyzed for IL-1alpha, its soluble receptor (sIL-1RII), receptor antagonist (IL-1Ra), interleukin-6 (IL-6) and heat shock protein-70A (lysates only). Significant release of IL-1alpha and PGE2 was detected only above 43 degrees C, where viability deteriorated and histological damage (especially to keratinocytes) was observed. With both skin products, sIL-1RII release was heat-depressed. IL-1alpha and IL-1Ra were elevated in media and IL-1Ra appeared to lower the bioactivity of IL-1alpha. Heat depressed IL-6 release from Skin2 fibroblasts. IL-6 production and release were negligible with EpiDerm. Heat increased Hsp-70A in both products. We conclude keratinocytes and fibroblasts are not primary cytokine and prostaglandin sources in heatstroke (< 44 degrees C) but could be in evaporative cooling failure, focal hot spots, or systemic responses. Levels of IL-1Ra, PGE2 and Hsp70A may be important markers of cell status.
US Army Research Institute of Environmental Medicine, Military Nutrition and Biochemistry Division, Natick, MA 01760-5007, USA.
W
W
Bowers
M
M
Blaha
A
A
Alkhyyat
J
J
Sankovich
J
J
Kohl
G
G
Wong
D
D
Patterson
D034961:Antigens, Nuclear; D018797:Cell Cycle Proteins; D002470:Cell Survival; D015232:Dinoprostone / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006358:Hot Temperature; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D034521:Nuclear Matrix-Associated Proteins; D009687:Nuclear Proteins / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D053574:Receptors, Interleukin-1 Type II; D012795:Sialoglycoproteins / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000378:metabolism; D017768:Skin, Artificial; D012995:Solubility; D013929:Thromboxane B2 / Q000378:metabolism
D034961:Antigens, Nuclear; D018797:Cell Cycle Proteins; D018840:HSP70 Heat-Shock Proteins; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015850:Interleukin-6; C050045:NUMA1 protein, human; D034521:Nuclear Matrix-Associated Proteins; D009687:Nuclear Proteins; D011453:Prostaglandins; D017472:Receptors, Interleukin-1; D053574:Receptors, Interleukin-1 Type II; D012795:Sialoglycoproteins; D013929:Thromboxane B2; D015232:Dinoprostone