Sphingosine 1‐phosphate elicits a ROS‐mediated proinflammatory response in human endometrial stromal cells via ERK5 activation

• DOI: 10.1096/fj.202300323r
• Publication Date: 2023-06-30T15:44:12Z
• Authors: Isabelle Seidita; Ignazia Tusa; Matteo Prisinzano; Alessio Menconi; Francesca Cencetti; Silvia Vannuccini; Francesca Castigl...; Paola Bruni; Felice Petraglia; Caterina Bernacch...; Elisabetta Rovida; Chiara Donati
• Keywords: Proinflammatory cytokine; Sphingosine-1-phosphate receptor

Abstract Endometriosis is a chronic gynecological disease affecting ~10% women in the reproductive age characterized by growth of endometrial glands and stroma outside uterine cavity. The inflammatory process has key role initiation progression disorder. Currently, there are no available early diagnostic tests therapy relies exclusively on symptomatic drugs, so that elucidation complex molecular mechanisms involved pathogenesis endometriosis an unmet need. signaling bioactive sphingolipid sphingosine 1‐phosphate (S1P) deeply dysregulated endometriosis. S1P modulates variety fundamental cellular processes, including inflammation, neo‐angiogenesis, immune responses acting mainly as ligand family G‐protein‐coupled receptors named (S1PR), 1–5 . Here, we demonstrated mitogen‐activated protein kinase ERK5, expressed endometriotic lesions determined quantitative PCR, activated human stromal cells. S1P‐induced ERK5 activation was shown to be triggered 1/3 via SFK/MEK5‐dependent axis. was, turn, responsible for increase reactive oxygen species proinflammatory cytokine expression present findings indicate signaling, activation, supports response endometrium establish rationale exploitation innovative therapeutic targets