953 EGF is an important modulator of the release of the alarmin IL-33 by human keratinocytes
نویسندگان
چکیده
Background and aims: Etokimab (an anti-IL-33 biologic) has been shown to significantly reduced the clinical severity of atopic dermatitis (AD) in a Phase 2A trial, suggesting an important role for IL-33 pathogenesis this disease. We recently showed that epidermal growth factor receptor (EGFR) dominates signaling keratinocytes from adults with lesions. The aim study was investigate possible EGFR pathway modulating release human keratinocytes. Methods: effect EGF cetuximab anti-EGFR on Staphylococcus aureus secretome (SA)-induced induced keratinocytes, assessed vitro using RNAseq (synthesis), phosphoarray (cell signaling), ELISA Western blot (release). Inhibitors cellular pathways were added interrogate their release. Results: While promoted S. RNA synthesis at 6 hours, it blocked early constitutive by dose-dependent manner. There no cell viability. Cetuximab augmented aureus. addition SA stimulated altered phosphorylation EGFR, highlighting inhibitory Cetuximab, which is known inhibit phosphorylation, S Conclusions: modulator A better understanding events leading modulation alarmin may provide novel therapeutic targets dermatitis.
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ژورنال
عنوان ژورنال: Journal of Investigative Dermatology
سال: 2023
ISSN: ['1523-1747', '0022-202X']
DOI: https://doi.org/10.1016/j.jid.2023.03.964