Keratinocyte-Specific Deletion of the IL-6RA Exacerbates the Inflammatory Response During Irritant Contact Dermatitis

Details

• Personal Author:
  Calhoun KN ; Frempah B ; Gallucci RM ; Luckett-Chastain LR
• Description:
  Irritant Contact Dermatitis (ICD) is the most common occupational skin disorder. During ICD, keratinocytes initiate the inflammatory cascade by producing cytokines including IL-6. This laboratory previously reported that IL-6 deficiency exacerbates skin inflammation during ICD, yet the role of the IL-6Ra in keratinocyte function has yet to be elucidated. To investigate how IL-6Ra function in keratinocytes influences the inflammatory response during ICD, keratinocyte-specific IL-6Ra KO (IL6raAker) and WT mice were exposed to two well-known occupational irritants; JP-8 jet fuel, and benzalkonium chloride (BKC), or acetone control for three days. Dermatitis lesions were collected and flow cytometric and immunohistochemical analyses revealed that IL6raAker skin displayed increased populations of CD11b+CD45+ and F4/80+ cells respectively relative to WT. However, IL6raAker mouse skin contained reduced numbers of yo T cells relative to WT. Furthermore, IL6raAker skin expressed increased levels of pro-inflammatory cytokines including IL-1β, IL-22, and CCL4 but decreased levels of anti-inflammatory cytokines IL-4 and IL-10. These results indicate that epidermal keratinocyte IL-6Ra function modulates epidermal hyperplasia, immune cell infiltration into skin and cytokine expression during ICD and suggests that the previously reported protective effect of IL-6 during ICD might be mediated primarily by keratinocyte derived IL-6Ra. [Description provided by NIOSH]
• Subjects:
  Immune System Irritants Laboratories Occupational Health Pathology Safety Skin Skin Diseases
• Keywords:
  Author Keywords: Inflammation Contact Dermatitis Cytokines Immune Reaction Irritant Contact Dermatitis Jet Engine Fuels Keratinocytes Laboratory Animals Skin Disorders
• ISSN:
  0300-483X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Oklahoma ; OSHA Region 6
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  123-131
• Volume:
  423
• NIOSHTIC Number:
  nn:20056368
• Citation:
  Toxicology 2019 Jul; 423:123-131
• Contact Point Address:
  Randle M. Gallucci, OUHSC College of Pharmacy, P. O. Box 26901, Oklahoma City, OK 73126-0901
• 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):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:9cea59e7434ed8cce3ab7ebc4a1d3bdceee4a5cfac86f2d527f450b279c4145c721a28a49c2863a032ede4b8234a64d2734cb45dc3db2f7e34446e6628e87cd8
• Download URL:
  https://stacks.cdc.gov/view/cdc/213991/cdc_213991_DS1.pdf
• File Type:
  [PDF - 2.62 MB ]