Rifamycin SV exhibits strong anti-inflammatory in vitro activity through pregnane X receptor stimulation and NFκB inhibition
| Autor: | Caridad Rosette, Cesare Hassan, Luigi Moro, Mara Gerloni, Alessandro Mazzetti, Frances J. Agan, Niccolette Rosette |
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| Rok vydání: | 2019 |
| Předmět: |
Transcriptional Activation
Chemokine Cellular detoxification Anti-Inflammatory Agents Cell Culture Techniques Pharmaceutical Science Pharmacology digestive system 030226 pharmacology & pharmacy 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine polycyclic compounds Cytochrome P-450 CYP3A Humans Pharmacology (medical) ATP Binding Cassette Transporter Subfamily B Member 1 Interleukin 8 030304 developmental biology 0303 health sciences Pregnane X receptor biology Ansamycin NF-kappa B Pregnane X Receptor Rifamycin Hep G2 Cells Rifamycins digestive system diseases Rifaximin chemistry biology.protein Tumor necrosis factor alpha Caco-2 Cells HT29 Cells Signal Transduction |
| Zdroj: | Drug Metabolism and Pharmacokinetics. 34:172-180 |
| ISSN: | 1347-4367 |
| DOI: | 10.1016/j.dmpk.2019.01.002 |
| Popis: | 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 NFκB. 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 TNFα and LPS-induced NFκB activities and inhibited IL1β-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 NFκB 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 NFκB inhibition and concomitant IL8 inhibition. |
| Databáze: | OpenAIRE |
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