Acetaminophen-Induced Liver Injury Exposes Murine IL-22 as Sex-Related Gene Product
| Autor: | Stülb, Hendrik, Bachmann, Malte, Gonther, Sina, Mühl, Heiko |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Lipopolysaccharides
Male QH301-705.5 T-Lymphocytes Gene Expression Adaptive Immunity Article Mice Sex Factors Cell Line Tumor Basic Helix-Loop-Helix Transcription Factors gender Animals sex ddc:610 Biology (General) QD1-999 acetaminophen Interleukins interleukin-22 Dihydrotestosterone Immunity Innate Mice Inbred C57BL Disease Models Animal Chemistry Receptors Aryl Hydrocarbon inflammation liver damage testosterone Female Chemical and Drug Induced Liver Injury Spleen Signal Transduction |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 10623, p 10623 (2021) International Journal of Molecular Sciences Volume 22 Issue 19 |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | Gaining detailed knowledge about sex-related immunoregulation remains a crucial prerequisite for the development of adequate disease models and therapeutic strategies enabling personalized medicine. Here, the key parameter of the production of cytokines mediating disease resolution was investigated. Among these cytokines, STAT3-activating interleukin (IL)-22 is principally associated with recovery from tissue injury. By investigating paradigmatic acetaminophen-induced liver injury, we demonstrated that IL-22 expression is enhanced in female mice. Increased female IL-22 was confirmed at a cellular level using murine splenocytes stimulated by lipopolysaccharide or αCD3/CD28 to model innate or adaptive immunoactivation. Interestingly, testosterone or dihydrotestosterone reduced IL-22 production by female but not by male splenocytes. Mechanistic studies on PMA/PHA-stimulated T-cell-lymphoma EL-4 cells verified the capability of testosterone/dihydrotestosterone to reduce IL-22 production. Moreover, we demonstrated by chromatin immunoprecipitation that testosterone impairs binding of the aryl hydrocarbon receptor to xenobiotic responsive elements within the murine IL-22 promoter. Overall, female mice undergoing acute liver injury and cultured female splenocytes upon inflammatory activation display increased IL-22. This observation is likely related to the immunosuppressive effects of androgens in males. The data presented concur with more pronounced immunological alertness demonstrable in females, which may relate to the sex-specific course of some immunological disorders. |
| Databáze: | OpenAIRE |
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