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Transcriptional Profiling of Irritant Contact Dermatitis (ICD) in a Mouse Model Identifies Specific Patterns of Gene Expression and Immune-Regulation



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  • Personal Author:
  • Description:
    Background: Irritant contact dermatitis (ICD) is a cutaneous inflammatory response to a variety of triggers that requires no sensitization and accounts for up to 80% of occupational dermatitis cases. IL-6 has been alternately associated with both allergic and irritant dermatitis and is closely linked to skin wound healing, therefore making it an ideal candidate to investigate in the mechanism of ICD. Results: Despite being a well-known pro-inflammatory cytokine, IL-6 deficient (IL-6KO) mice show much more severe ICD than controls. Transcriptome analysis was employed to examine irritant-exposed and control skin samples from C57BL/6 and IL-6KO mice. Over 1900 transcripts were found differentially modulated between C57 (1184 total) and IL-6KO (802 total) mice with the magnitude of expression significantly disparate. Overall gene ontology revealed metabolic and cellular enriched functional processes but numerous pro-inflammatory and immune associated genes (Cxcl2, Cxcl3, Cxcl5, Acod, Hamp, c-Lectins, for example), keratin associated genes (Krt6b and various Krtaps), and members of the Sprr and Lce family, which promote skin barrier integrity and keratinocyte functions, were also differentially modulated. Conclusions: The altered expression of these genes may provide a potential mechanism to explain the increased ICD severity in IL-6-deficient mice. Overall, this study offers new insight into the pathogenesis of ICD, indicates new mediators/biomarkers that may influence the variability of responses to irritants and provides potential targets for therapeutic development. [Description provided by NIOSH]
  • Subjects:
  • Keywords:
  • ISSN:
    0300-483X
  • Document Type:
    Text
  • Funding:
    Grant
  • Genre:
    Journal Article
  • Place as Subject:
  • CIO:
    National Institute for Occupational Safety and Health (NIOSH)
  • Topic:
    Workplace Safety & Health
  • Location:
    North America
  • Pages in Document:
    1-9
  • Volume:
    410
  • NIOSHTIC Number:
    nn:20054210
  • Citation:
    Toxicology 2018 Dec; 410:1-9
  • Contact Point Address:
    Randle M. Gallucci, OUHSC College of Pharmacy, 1110 N. Stonewall, Rm 333, Oklahoma City, OK, 73117, United States
  • Email:
    randy-gallucci@ouhsc.edu
  • Federal Fiscal Year:
    2019
  • Performing Organization:
    University of Oklahoma Health Sciences Center, Oklahoma City
  • Peer Reviewed:
    True
  • Start Date:
    20130901
  • Source Full Name:
    Toxicology
  • End Date:
    20180831
  • Collection(s):
  • Main Document Checksum:
    urn:sha-512:2408180017a48d7eb5dce5389b5e2d79ada91692c8c922b8f8047402df64329ab6d3acbac1572f8ee7437599addca855a3e44e7f53035e3a4af795b4b5cf3cba
  • Download URL:
  • File Type:
    Filetype[PDF - 1.48 MB ]
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