Analysis of amphotericin B-induced cell signaling with chemical inhibitors of signaling molecules

Microbiology and Immunology
Kenichiro MatsuoKoji Nakayama

Abstract

Although amphotericin B (AmB) is a major polyene antibiotic against invasive fungal infection, administration to patients sometimes causes inflammatory side effects, which limits the usage of the antibiotic. We studied the intracellular signaling that was induced by AmB. p65 (RelA) of nuclear factor-kappaB (NF-kappaB), a well-known signaling molecule as an inducer of proinflammatory cytokines, was phosphorylated by AmB in RAW264.7 cells, a monocyte-like cell line. Among chemical inhibitors of signaling molecules, U-73122 (phospholipase C (PLC) inhibitor), Gö6976 (protein kinase C (PKC) inhibitor), BAPTA-AM (calcium chelator), LFM-A13 (Bruton's tyrosine kinase (Btk)-specific inhibitor), and PP2 (c-Src kinase inhibitor) suppressed AmB-induced phosphorylation of p65 and translocation of p65 into the nucleus. U-73122 and Gö6976 reduced AmB-mediated induction of proinflammatory cytokines (tumor necrosis factor (TNF)-alpha and interleukin (IL)-6) in RAW264.7 cells. Furthermore, AmB-induced activation of NF-kappaB was observed in toll-like receptor (TLR) 2-expressed cells, and the activation of NF-kappaB was inhibited by U-73122, whereas peptidoglycan-induced NF-kappaB activation, which was also dependent on TLR2, was not inhibited by...Continue Reading

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Citations

Jun 1, 2011·Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology·Hideko KanTaisaku Amakawa
Mar 29, 2014·Frontiers in Microbiology·Mircea R MihuJoshua D Nosanchuk
Apr 28, 2012·Journal of Dental Research·R TamaiY Kiyoura
Feb 27, 2008·International Reviews of Immunology·Fatih M Uckun
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Sep 20, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·I-Ta LeeChuen-Mao Yang
Jul 9, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Antara BanerjeeNahid Ali

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