1. IL-6 Negatively Regulates IL-22R α Expression on Epidermal Keratinocytes: Implications for Irritant Contact Dermatitis.
- Author
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Frempah B, Luckett-Chastain LR, and Gallucci RM
- Subjects
- Animals, Biomarkers, Disease Models, Animal, Epidermis immunology, Immunohistochemistry, Mice, Dermatitis, Contact etiology, Dermatitis, Contact metabolism, Epidermis metabolism, Gene Expression Regulation, Interleukin-6 metabolism, Irritants adverse effects, Keratinocytes metabolism, Receptors, Interleukin genetics
- Abstract
Irritant Contact Dermatitis (ICD) is characterized by epidermal hyperplasia and inflammatory cytokine release. IL-6 has been shown to be involved in the pathogenesis of ICD; however, the involvement of the IL-22/IL-22R α axis and its relation to IL-6 in the inflammatory response following irritant exposure are unknown. Using a chemical model of ICD, it was observed that mice with a keratinocyte-specific knockout of IL-6R α (IL-6R α
Δker ) presented with increased inflammation and IL-22R α and IL-22 protein expression relative to WT following irritant exposure, indicating that IL-6R α deficiency in epidermal keratinocytes leads to the upregulation of IL-22R α and its ligand during ICD. Furthermore, it was shown that IL-6 negatively regulates the expression of IL-22R α on epidermal keratinocytes. This effect is functional as the effects of IL-22 on keratinocyte proliferation and differentiation were markedly reduced when keratinocytes were pretreated with IL-6 prior to IL-22 treatment. These results show that IL-6 modulates the IL-22/IL-22R α axis in the skin and suggest that this occurrence may be associated with the increased epidermal hyperplasia and exacerbated inflammatory response observed in IL-6R αΔker mice during ICD., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 Benjamin Frempah et al.)- Published
- 2019
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