PMID: 11907163Mar 22, 2002Paper

Inhibitors of ATP-binding cassette transporters suppress interleukin-12 p40 production and major histocompatibility complex II up-regulation in macrophages

The Journal of Pharmacology and Experimental Therapeutics
György HaskóCsaba Szabó

Abstract

ATP-binding cassette (ABC) transporters are a large family of proteins whose role is to translocate various substances across biological membranes. They include the Tangier disease protein ABC1, sulfonylurea receptors (SUR), multidrug resistance protein (MDR), and cystic fibrosis transmembrane regulator (CFTR). In the current study, we investigated the involvement of ABC transporters in the regulation of lipopolysaccharide (LPS) and/or interferon (IFN)-gamma-induced interleukin (IL)-12 p40 and tumor necrosis factor (TNF)-alpha production, nitric oxide formation, as well as major histocompatibility complex II up-regulation in macrophages. The general ABC transporter inhibitor glibenclamide suppressed both IL-12 p40 and nitric oxide production. However, glibenclamide failed to affect the production of TNF-alpha. The selective ABC1 inhibitors 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid and sulfobromophthalein mimicked the suppressive effect of glibenclamide on IL-12 p40 production. On the other hand, both the MDR inhibitor verapamil and CFTR blocker 2,2'-iminodibenzoic acid failed to suppress the production of IL-12 p40. Furthermore, selective inhibitors and activators of SURs were without effect. In agreement with the pharma...Continue Reading

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Citations

Jan 30, 2013·PloS One·Sanhita RoyAlan M Tartakoff
Feb 5, 2011·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Gavin C K W KohSharon J Peacock
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