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Effects of CEES on inflammatory mediators, heat shock protein 70A, histology and ultrastructure in two skin models † **
Author(s) -
Blaha M.,
Bowers W.,
Kohl J.,
DuBose D.,
Walker J.,
Alkhyyat A.,
Wong G.
Publication year - 2000
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/1099-1263(200012)20:1+<::aid-jat672>3.0.co;2-r
Subject(s) - extracellular , histology , chemistry , interleukin , ultrastructure , fibroblast , viability assay , andrology , microbiology and biotechnology , biology , pathology , immunology , biochemistry , cytokine , medicine , anatomy , cell , in vitro
Chemical warfare threats require the development of diverse models for the assessment of countermeasures. Human skin products, Skin 2® (differentiating keratinocytes on a fibroblast‐collagen matrix) and EpiDerm ® (differentiating keratinocytes) were exposed (2 h) to the sulfur mustard 2‐chloroethyl ethyl sulfide (CEES, 1‐2 mg l −1 min −1 ) in humidified air or to humidified air alone. Tissues were evaluated histologically, ultrastructurally and for viability 22 h later; media and tissues were also analyzed for inflammatory mediators. Histology showed that CEES induced the separation of dermal and epidermal regions in Skin 2 with severe damage to basal keratinocytes. Histology and electron microscopy of both products revealed condensation of nuclear chromatin, retraction of spinous processes, collapse of the tonofibrillar network and cytoplasmic vacuolization and blebbing in those cells with loss of pseudobasement membrane integrity. Exposure of Skin 2 to CEES increased extracellular interleukin‐1α (IL‐1α), prostaglandin‐E 2 (PGE 2 ) and especially IL‐1 receptor antagonist (IL‐1Ra) release (56334 vs 84 614 pg ml −1 ), but decreased interleukin‐6 (IL−6, 4755 vs 351 pg ml −1 ). Exposure of EpiDerm to CEES led to unaffected extracellular and reduced intracellular IL−1α (371 vs 92 pg m1 −1 ). Extracellular IL‐1Ra greatly increased (2375 vs 24875 pg ml −1 ), whereas cellular levels decreased (165425 vs 96625 pg ml −1 ). Extracellular (224 vs 68 pg ml −1 ) and intracellular (485 vs 233 pg ml −1 ) soluble interleukin‐1 receptor II (sIL‐1RII) decreased. Prostanglandin E 2 increased (1835 vs 2582 pg ml −1 ), whereas heat shock protein 70A (Hsp70A) remained statistically unchanged (57000 vs 96000 pg ml −1 ). Failure to obtain a heat shock response to CEES may contribute to the susceptibility of tissue to the alkylating agent. Consistent and marked responses of cellular and extracellular IL‐1Ra to CEES suggest a potential for use as a tissue status marker and primary antiinflammatory regulator in skin. Published in 2000 by John Wiley & Sons, Ltd.