PT  - JOURNAL ARTICLE
AU  - Rana El Sabeh
AU  - Mélanie Bonnet
AU  - Katy Le Corf
AU  - Kevin Lang
AU  - Alain Kfoury
AU  - Bassam Badran
AU  - Nader Hussein
AU  - François Virard
AU  - Isabelle Treilleux
AU  - Muriel Le Romancer
AU  - Serge Lebecque
AU  - Serge Manié
AU  - Isabelle Coste
AU  - Toufic Renno
TI  - A Gender-Dependent Molecular Switch of Inflammation <em>via</em> MyD88/Estrogen Receptor-alpha Interaction
AID  - 10.1101/255778
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 255778
4099  - http://biorxiv.org/content/early/2018/01/31/255778.short
4100  - http://biorxiv.org/content/early/2018/01/31/255778.full
AB  - 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. Here 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. 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.