Matches in SemOpenAlex for { <https://semopenalex.org/work/W3212353708> ?p ?o ?g. }
- W3212353708 abstract "Mucosal epithelial cell integrity is an important component of innate immunity and it protects the host from an environment rich in microorganisms. Virulence factors from Gram-negative bacteria [e.g. lipopolysaccharide (LPS)] induce significant pro-inflammatory cytokine expression. Monoamine oxidase (MAO) inhibitors reduce cytokine expression in a variety of inflammatory models and may therefore have therapeutic potential for a number of inflammatory diseases. We tested the anti-inflammatory therapeutic potential of a recently developed reversible MAO-B inhibitor (RG0216) with reduced transport across the blood-brain barrier. In an epithelial cell culture model, RG0216 significantly decreased LPS-induced interleukin (IL)-6 and IL-1β gene and protein expression and was as effective as equimolar concentrations of deprenyl (an existing irreversible MAO-B inhibitor). Hydrogen peroxide and modulating dopamine receptor signaling had no effect on cytokine expression. We showed that LPS-induced expression of IL-6 and IL-1β was cAMP dependent, that IL-6 and IL-1β expression were induced by direct cAMP activation (forskolin) and that RG0216 and deprenyl effectively reduced cAMP-mediated cytokine expression. Targeted protein kinase A (PKA) and Exchange Protein Activated by cAMP (EPAC) activation regulated IL-6 and IL-1β expression, albeit in different ways, but both cytokines were effectively decreased with RG0216. RG0216 reduction of LPS-induced cytokine expression occurred by acting downstream of the cAMP-PKA/EPAC signaling cascade. This represents a novel mechanism by which MAO-B selective inhibitors regulate LPS-induced IL-6 and IL-1β expression." @default.
- W3212353708 created "2021-11-22" @default.
- W3212353708 creator A5003788718 @default.
- W3212353708 creator A5013595624 @default.
- W3212353708 creator A5036345252 @default.
- W3212353708 date "2021-11-17" @default.
- W3212353708 modified "2023-10-14" @default.
- W3212353708 title "Monoamine Oxidase-B Inhibitor Reduction in Pro-Inflammatory Cytokines Mediated by Inhibition of cAMP-PKA/EPAC Signaling" @default.
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- W3212353708 doi "https://doi.org/10.3389/fphar.2021.741460" @default.
- W3212353708 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34867348" @default.
- W3212353708 hasPublicationYear "2021" @default.
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