Rifamycin SV (rifamycin), is a member of the ansamycin family of antimicrobial compounds which kills bacteria commonly associated with infectious diarrhea and other enteric infections. Rifamycin has been found to be effective in experimental animal models of gut inflammation and its efficacy in these settings has been attributed partially to immunomodulatory non-bactericidal activities. This study aimed to further evaluate the anti-inflammatory activities of rifamycin by analyzing its effect on two key regulators of inflammation: PXR and NFkB. Rifamycin stimulated PXR transcriptional activity in two PXR reporter cell lines and induced expression of two genes known to be regulated by PXR and are directly involved in cellular detoxification: CYP3A4 and PgP. Moreover, CYP3A4 metabolic activity was induced by rifamycin in HepG2 cells. Rifamycin also antagonized TNFa and LPS-induced NFkB activities and inhibited IL1b-induced synthesis of inflammatory chemokine, IL8. Although reciprocal regulation of PXR and NFkB by rifamycin was not directly addressed, the data suggest that in the absence of PXR, inhibition of NFkB
by rifamycin is not dependent on PXR stimulation. Thus, rifamycin exhibits potent anti-inflammatory activities, characterized by in vitro PXR activation and concomitant CYP3A4 and PgP induction, in parallel with potent NFkB inhibition and concomitant IL8 inhibition
To view the full article click HERE.
Date of publication: 8 January 2019; Drug Metabolism & Pharmacokinetics
Author information: Cadidad Rosette (1); Frances J. Agan (1); Niccolette Rosette (1); Luigi Moro (1); Alessandro Mazzetti (1); Cesare Hassan (2); & Mara Gerloni (1)
(1) Cosmo Pharmaceuticals, Riverside II, Sir John Rogerson’s Quay, Dublin 2, Ireland
(2) Nuovo Regina Margherita Hospital, Endoscopy Unit, Via e Morosini 30, Rome, 00153, Italy