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Misoprostol, prostaglandin analogue, modulates cytokine activity through cAMP pathway
Author(s) -
Gobejishvili Leila,
Barve Shirish,
Khan Rehan,
Avila Diana,
McClain Craig,
Hill Daniell
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb536
Subject(s) - misoprostol , cytokine , medicine , pharmacology , peripheral blood mononuclear cell , ex vivo , mifepristone , immunology , in vivo , biology , in vitro , pregnancy , biochemistry , genetics , microbiology and biotechnology , abortion
Dysregulated cytokine metabolism plays a critical role in the pathogenesis of alcoholic liver disease. We and others have shown that cAMP signaling critically modulates endotoxin‐stimulated expression of pro‐inflammatory cytokine TNF in monocytes and macrophages. The overall aim of this pilot study was to assess the efficacy of Misoprostol, as a potential therapeutic agent, in the treatment of alcoholic hepatitis (AH). Healthy volunteers were given different doses of Misoprostol and baseline and LPS‐inducible cytokine levels were examined ex vivo. Additionally, human peripheral blood mononuclear cells and murine macrophage cell line 264.7 were used to investigate underlying mechanisms of misoprostol effect on cytokine expression. Our results show that lower dose of Misoprostol was well‐tolerated with fewer GI side effects and was effective in modulating cytokine activity. Mechanistically, Misoprostol effect was critically mediated by increase in cAMP levels and consequent changes in activity of transcription factors CRE and NFκB. Further studies are needed to evaluate the effects of Misoprostol on the modulation of cytokine activity, liver function and clinical course in AH patients.