IL-6 Negatively Regulates IL-22Rα Expression on Epidermal Keratinocytes: Implications for Irritant Contact Dermatitis
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-22Rα axis and its relation to IL-6 in the inflammatory response following irritant ex...
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doaj-03e328c903604501939ada1633689ad12020-11-25T01:34:56ZengHindawi LimitedJournal of Immunology Research2314-88612314-71562019-01-01201910.1155/2019/62762546276254IL-6 Negatively Regulates IL-22Rα Expression on Epidermal Keratinocytes: Implications for Irritant Contact DermatitisBenjamin Frempah0Lerin R. Luckett-Chastain1Randle M. Gallucci2Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, 1110 N. Stonewall Avenue, Oklahoma City, OK 73117, USADepartment of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, 1110 N. Stonewall Avenue, Oklahoma City, OK 73117, USADepartment of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, 1110 N. Stonewall Avenue, Oklahoma City, OK 73117, USAIrritant 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-22Rα 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-6Rα (IL-6RαΔker) presented with increased inflammation and IL-22Rα and IL-22 protein expression relative to WT following irritant exposure, indicating that IL-6Rα deficiency in epidermal keratinocytes leads to the upregulation of IL-22Rα and its ligand during ICD. Furthermore, it was shown that IL-6 negatively regulates the expression of IL-22Rα 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-22Rα axis in the skin and suggest that this occurrence may be associated with the increased epidermal hyperplasia and exacerbated inflammatory response observed in IL-6RαΔker mice during ICD.http://dx.doi.org/10.1155/2019/6276254 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Benjamin Frempah Lerin R. Luckett-Chastain Randle M. Gallucci |
spellingShingle |
Benjamin Frempah Lerin R. Luckett-Chastain Randle M. Gallucci IL-6 Negatively Regulates IL-22Rα Expression on Epidermal Keratinocytes: Implications for Irritant Contact Dermatitis Journal of Immunology Research |
author_facet |
Benjamin Frempah Lerin R. Luckett-Chastain Randle M. Gallucci |
author_sort |
Benjamin Frempah |
title |
IL-6 Negatively Regulates IL-22Rα Expression on Epidermal Keratinocytes: Implications for Irritant Contact Dermatitis |
title_short |
IL-6 Negatively Regulates IL-22Rα Expression on Epidermal Keratinocytes: Implications for Irritant Contact Dermatitis |
title_full |
IL-6 Negatively Regulates IL-22Rα Expression on Epidermal Keratinocytes: Implications for Irritant Contact Dermatitis |
title_fullStr |
IL-6 Negatively Regulates IL-22Rα Expression on Epidermal Keratinocytes: Implications for Irritant Contact Dermatitis |
title_full_unstemmed |
IL-6 Negatively Regulates IL-22Rα Expression on Epidermal Keratinocytes: Implications for Irritant Contact Dermatitis |
title_sort |
il-6 negatively regulates il-22rα expression on epidermal keratinocytes: implications for irritant contact dermatitis |
publisher |
Hindawi Limited |
series |
Journal of Immunology Research |
issn |
2314-8861 2314-7156 |
publishDate |
2019-01-01 |
description |
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-22Rα 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-6Rα (IL-6RαΔker) presented with increased inflammation and IL-22Rα and IL-22 protein expression relative to WT following irritant exposure, indicating that IL-6Rα deficiency in epidermal keratinocytes leads to the upregulation of IL-22Rα and its ligand during ICD. Furthermore, it was shown that IL-6 negatively regulates the expression of IL-22Rα 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-22Rα axis in the skin and suggest that this occurrence may be associated with the increased epidermal hyperplasia and exacerbated inflammatory response observed in IL-6RαΔker mice during ICD. |
url |
http://dx.doi.org/10.1155/2019/6276254 |
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