International journal of molecular sciences, 2021-09, Vol.22 (19), p.10623
2021
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- Autor(en) / Beteiligte
- Titel
- Acetaminophen-Induced Liver Injury Exposes Murine IL-22 as Sex-Related Gene Product
- Ist Teil von
- International journal of molecular sciences, 2021-09, Vol.22 (19), p.10623
- Ort / Verlag
- Switzerland: MDPI AG
- Erscheinungsjahr
- 2021
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1422-0067, 1661-6596eISSN: 1422-0067DOI: 10.3390/ijms221910623Titel-ID: cdi_doaj_primary_oai_doaj_org_article_5b449d759a1e400a87df5983de483d2d
- Format
- –
- Schlagworte
- Acetaminophen, Acetaminophen - adverse effects, Acetaminophen - blood, Adaptive Immunity - drug effects, Alertness, Analgesics, Androgens, Animals, Basic Helix-Loop-Helix Transcription Factors - metabolism, CD28 antigen, Cell Line, Tumor, Chemical and Drug Induced Liver Injury - blood, Chemical and Drug Induced Liver Injury - genetics, Chemical and Drug Induced Liver Injury - metabolism, Chromatin, Cytokines, Dihydrotestosterone, Dihydrotestosterone - pharmacology, Disease Models, Animal, Experiments, Female, Females, gender, Gene expression, Gene Expression - drug effects, Immunity, Innate - drug effects, Immunology, Immunoprecipitation, Immunoregulation, Inflammation, Inflammation - chemically induced, Inflammation - immunology, Interleukin 22, Interleukins - genetics, Interleukins - metabolism, Lipopolysaccharides, Lipopolysaccharides - adverse effects, Liver, Lymphocytes, Lymphocytes T, Lymphoma, Male, Males, Mice, Mice, Inbred C57BL, Precision medicine, Receptors, Aryl Hydrocarbon - metabolism, sex, Sex Factors, Sexes, Signal Transduction - drug effects, Spleen - cytology, Spleen - metabolism, Splenocytes, Stat3 protein, T cell receptors, T-Lymphocytes - drug effects, T-Lymphocytes - metabolism, Testosterone, Testosterone - pharmacology, Tumor necrosis factor-TNF