Natural Product Anacardic Acid from Cashew Nut Shells Stimulates Neutrophil Extracellular Trap Production and Bactericidal Activity.

Autor:	Hollands A; Department of Pediatrics, University of California, San Diego, La Jolla, California 920934., Corriden R; Department of Pharmacology, University of California, San Diego, La Jolla, California 92093., Gysler G; Department of Pediatrics, University of California, San Diego, La Jolla, California 920934., Dahesh S; Department of Pediatrics, University of California, San Diego, La Jolla, California 920934., Olson J; Department of Pediatrics, University of California, San Diego, La Jolla, California 920934., Raza Ali S; Department of Pediatrics, University of California, San Diego, La Jolla, California 920934., Kunkel MT; Department of Pharmacology, University of California, San Diego, La Jolla, California 92093., Lin AE; Department of Pediatrics, University of California, San Diego, La Jolla, California 920934., Forli S; Department of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, California 92037., Newton AC; Department of Pharmacology, University of California, San Diego, La Jolla, California 92093., Kumar GB; School of Biotechnology, Amrita University, Kollam, 690525 Kerala, India., Nair BG; School of Biotechnology, Amrita University, Kollam, 690525 Kerala, India., Perry JJP; School of Biotechnology, Amrita University, Kollam, 690525 Kerala, India; Department of Biochemistry, University of California, Riverside, California 92521., Nizet V; Department of Pediatrics, University of California, San Diego, La Jolla, California 920934; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California 92093,. Electronic address: vnizet@ucsd.edu.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2016 Jul 01; Vol. 291 (27), pp. 13964-13973. Date of Electronic Publication: 2016 May 13.
DOI:	10.1074/jbc.M115.695866
Abstrakt:	Emerging antibiotic resistance among pathogenic bacteria is an issue of great clinical importance, and new approaches to therapy are urgently needed. Anacardic acid, the primary active component of cashew nut shell extract, is a natural product used in the treatment of a variety of medical conditions, including infectious abscesses. Here, we investigate the effects of this natural product on the function of human neutrophils. We find that anacardic acid stimulates the production of reactive oxygen species and neutrophil extracellular traps, two mechanisms utilized by neutrophils to kill invading bacteria. Molecular modeling and pharmacological inhibitor studies suggest anacardic acid stimulation of neutrophils occurs in a PI3K-dependent manner through activation of surface-expressed G protein-coupled sphingosine-1-phosphate receptors. Neutrophil extracellular traps produced in response to anacardic acid are bactericidal and complement select direct antimicrobial activities of the compound. (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)
Databáze:	MEDLINE
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