Clotrimazole ameliorates intestinal inflammation and abnormal angiogenesis by inhibiting interleukin-8 expression through a nuclear factor-kappaB-dependent manner

The Journal of Pharmacology and Experimental Therapeutics
Dinesh ThapaJung-Ae Kim

Abstract

Increased interleukin (IL)-8 plays an important role not only in activation and recruitment of neutrophils but also in inducing exaggerated angiogenesis at the inflamed site. In the present study, we investigated the fact that clotrimazole (CLT) inhibits intestinal inflammation, and the inhibitory action is mediated through suppression of IL-8 expression. In the trinitrobenzene sulfonic acid (TNBS)-induced rat colitis model, CLT dose-dependently protected from the TNBS-induced weight loss, colon ulceration, and myeloperoxidase activity increase. In the lesion site, CLT also suppressed the TNBS-induced angiogenesis, IL-8 expression, and nuclear factor (NF)-kappaB activation. In a cellular model of colitis using tumor necrosis factor (TNF)-alpha-stimulated HT29 colon epithelial cells, treatment with CLT significantly suppressed TNF-alpha-mediated IL-8 induction and NF-kappaB transcriptional activity revealed by a luciferase reporter gene assay. Furthermore, cotreatment with CLT and pyrrolidine dithiocarbamate, a NF-kappaB inhibitor, synergistically reduced the NF-kappaB transcriptional activity as well as IL-8 expression. In an in vitro angiogenesis assay, CLT suppressed IL-8-induced proliferation, tube formation, and invasion of...Continue Reading

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Citations

Jul 31, 2013·Inflammation·Arif Burak CekicCengiz Erçin
May 2, 2009·Archives of Pharmacal Research·Dinesh ThapaJung-Ae Kim
Aug 7, 2012·Archives of Pharmacal Research·Prabagar BalakrishnanHan-Gon Choi
Sep 17, 2009·The American Journal of Gastroenterology·Udayakumar Navaneethan, Bo Shen
Jul 31, 2013·Antimicrobial Agents and Chemotherapy·Duncan WilsonBernhard Hube
Nov 3, 2010·Alimentary Pharmacology & Therapeutics·S SamuelW J Sandborn
Apr 16, 2010·Biology of Reproduction·Nicoletta Di SimoneRiccardo Marana
Aug 4, 2020·Bioorganic Chemistry·Chhabi Lal ChaudharyByeong-Seon Jeong
May 3, 2011·Developmental and Comparative Immunology·Xianwei CuiShuangquan Zhang

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