A Gender-Dependent Molecular Switch of Inflammation via MyD88/Estrogen Receptor-Alpha Interaction
Autor: | Alain Kfoury, Isabelle Coste, Muriel Le Romancer, Melanie Bonnet, François Virard, Isabelle Treilleux, Kevin Lang, Serge Manié, Toufic Renno, Bassam Badran, Serge Lebecque, Rana El Sabeh, Nader Hussein, Katy Le Corf |
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Přispěvatelé: | Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], Université Libanaise, Coste, Isabelle, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Chemokine protein-protein-interaction medicine.drug_class medicine.medical_treatment [SDV]Life Sciences [q-bio] Immunology Estrogen receptor Inflammation Proximity ligation assay 03 medical and health sciences 0302 clinical medicine medicine Immunology and Allergy nuclear receptor Receptor ComputingMilieux_MISCELLANEOUS Original Research 030304 developmental biology 0303 health sciences biology Chemistry Mechanism (biology) 3. Good health Cell biology [SDV] Life Sciences [q-bio] 030104 developmental biology Cytokine Nuclear receptor post-translational modification Estrogen Cytoplasm inflammation 030220 oncology & carcinogenesis biology.protein medicine.symptom Cell activation Journal of Inflammation Research Estrogen receptor alpha 030217 neurology & neurosurgery |
Zdroj: | Journal of Inflammation Research Journal of Inflammation Research, 2021, 14, pp.2149-2156. ⟨10.2147/JIR.S306805⟩ Journal of Inflammation Research, Dove Medical Press, 2021, Volume 14, pp.2149-2156. ⟨10.2147/JIR.S306805⟩ |
ISSN: | 1178-7031 |
Popis: | Rana El Sabeh,1,2 Mélanie Bonnet,1 Katy Le Corf,1 Kevin Lang,1 Alain Kfoury,1 Bassam Badran,2 Nader Hussein,2 Francois Virard,1 Isabelle Treilleux,3 Muriel Le Romancer,1 Serge Lebecque,1 Serge Manie,1 Isabelle Coste,1,* Toufic Renno1,* 1Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, France; 2Université Libanaise, PRASE, Hadath, Lebanon; 3Pathology Department, Centre Léon Bérard, Lyon, France*These authors contributed equally to this workCorrespondence: Toufic Renno; Isabelle CosteCentre de Recherche en Cancétologie de Lyon, 28 Rue Laennec, Lyon, 69373, FranceTel +33 4 691 666 29; +33 4 691 666 30Email toufic.renno@lyon.unicancer.fr ; isabelle.coste@lyon.unicancer.frIntroduction: Most Toll-like receptors and IL-1/IL-18 receptors activate a signaling cascade via the adaptor molecule MyD88, resulting in NF-κB activation and inflammatory cytokine and chemokine production. Females are less susceptible than males to inflammatory conditions, presumably due to protection by estrogen. The exact mechanism underlying this protection is unknown.Methods: MCF7 cells expressing wild-type or mutated LXXLL motif were used to determine MyD88/estrogen receptor (ER)-a interaction by immunoprecipitation and cell activation by ELISA and luciferase reporter assay. IL-1b and/or E2 were used to activate MCF7 cells expressing normal or knocked down levels of PRMT1. Finally, in situ proximity ligation assay with anti-MyD88 and anti-methylated ER-a (methER-a) antibodies was used to evaluate MyD88/methylated ER-a interaction in THP1 cells and histological sections.Results: We show that MyD88 interacts with a methylated, cytoplasmic form of estrogen receptor-alpha (methER-α). This interaction is required for NF-κB transcriptional activity and pro-inflammatory cytokine production, and is dissociated by estrogen. Importantly, we show a strong gender segregation in gametogenic reproductive organs, with MyD88/methER-α interactions found in testicular tissues and in ovarian tissues from menopausal women, but not in ovaries from women age 49 and less – suggesting a role for estrogen in disrupting this complex in situ.Discussion: Collectively, our results indicate that the formation of MyD88/methER-α complexes during inflammatory signaling and their disruption by estrogen may represent a mechanism that contributes to gender bias in inflammatory responses.Keywords: nuclear receptor, post-translational modification, inflammation, protein-protein-interaction |
Databáze: | OpenAIRE |
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