title: Crotamine stimulates phagocytic activity by inducing nitric oxide and TNF-α via p38 and NFκ-B signaling in RAW 264.7 macrophages.
abstract: Crotamine is a peptide toxin found in the venom of the rattlesnake Crotalus durissus terrificus and has antiproliferative, antimicrobial, and antifungal activities. Herein, we show that crotamine dose-dependently induced macrophage phagocytic and cytostatic activity by the induction of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α). Moreover, the crotamineinduced expression of iNOS and TNF-α is mediated through the phosphorylation of p38 and the NF-κB signaling cascade in macrophages. Notably, pretreatment with SB203580 (a p38-specific inhibitor) or BAY 11-7082 (an NF-κB inhibitor) inhibited crotamine-induced NO production and macrophage phagocytic and cytotoxic activity. Our results show for the first time that crotamine stimulates macrophage phagocytic and cytostatic activity by induction of NO and TNF-α via the p38 and NF-κB signaling pathways and suggest that crotamine may be a useful therapeutic agent for the treatment of inflammatory disease. [BMB Reports 2016; 49(3): 185-190].
authors.affiliation: Department of Convergence Medicine, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea.
authors.forename: Kyung Jin
authors.initials: KJ
authors.lastname: Lee
authors.affiliation: Department of Convergence Medicine, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea.
authors.forename: Yun Kyu
authors.initials: YK
authors.lastname: Kim
authors.affiliation: Department of Physiology and Bio-Medical Institute of Technology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea.
authors.forename: Martin
authors.initials: M
authors.lastname: Krupa
authors.affiliation: Department of Physiology and Bio-Medical Institute of Technology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea.
authors.forename: Anh Ngoc
authors.initials: AN
authors.lastname: Nguyen
authors.affiliation: Department of Physiology and Bio-Medical Institute of Technology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea.
authors.forename: Bich Hang
authors.initials: BH
authors.lastname: Do
authors.affiliation: Department of Physiology and Bio-Medical Institute of Technology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea.
authors.forename: Boram
authors.initials: B
authors.lastname: Chung
authors.affiliation: Department of Physiology and Bio-Medical Institute of Technology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea.
authors.forename: Thi Thu Trang
authors.initials: TT
authors.lastname: Vu
authors.affiliation: Department of Surgery, Division of Hepatobilopancreatic Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea.
authors.forename: Song Cheol
authors.initials: SC
authors.lastname: Kim
authors.affiliation: Department of Physiology and Bio-Medical Institute of Technology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea.
authors.forename: Han
authors.initials: H
authors.lastname: Choe
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D003435:Crotalid Venoms / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D000067996:RAW 264.7 Cells; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D015533:Transcriptional Activation / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D003435:Crotalid Venoms; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C010563:crotamine; D052247:Nitric Oxide Synthase Type II; D048051:p38 Mitogen-Activated Protein Kinases
references.citation: FEMS Microbiol Lett. 2015 Jun;362(11):null
references.pmid: 25926528
references.citation: Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9407-11
references.pmid: 7937779
references.citation: Science. 1997 Jan 10;275(5297):200-3
references.pmid: 8985011
references.citation: J Bone Miner Res. 2015 Dec;30(12 ):2140-9
references.pmid: 26531055
references.citation: Biochem Biophys Res Commun. 2013 Feb 15;431(3):506-11
references.pmid: 23333393
references.citation: Biomed Res Int. 2014;2014:675985
references.pmid: 24551848
references.citation: Annu Rev Immunol. 1998;16:225-60
references.pmid: 9597130
references.citation: Toxicon. 2014 Dec 15;92:157-65
references.pmid: 25448388
references.citation: EMBO J. 2014 May 16;33(10):1117-33
references.pmid: 24596247
references.citation: Br J Pharmacol. 1978 Jul;63(3):551-9
references.pmid: 667499
references.citation: Annu Rev Immunol. 1997;15:323-50
references.pmid: 9143691
references.citation: Ther Apher Dial. 2003 Apr;7(2):252-8
references.pmid: 12918952
references.citation: Expert Opin Investig Drugs. 2011 Sep;20(9):1189-200
references.pmid: 21834748
references.citation: Expert Opin Investig Drugs. 2010 Dec;19(12):1515-25
references.pmid: 21062230
references.citation: Nat Rev Immunol. 2005 Oct;5(10):749-59
references.pmid: 16175180
references.citation: Science. 1987 Jan 23;235(4787):473-6
references.pmid: 2432665
references.citation: Biomed Pharmacother. 1994;48(10):445-53
references.pmid: 7858154
references.citation: Clin Biochem. 1997 Aug;30(6):455-63
references.pmid: 9316739
references.citation: Mol Cells. 2013 Feb;35(2):151-7
references.pmid: 23329300
references.citation: Mol Med Rep. 2015 Oct;12(4):5545-53
references.pmid: 26239044
references.citation: Cell Immunol. 2013 May-Jun;283(1-2):51-60
references.pmid: 23850963
references.citation: Toxicology. 2015 Jan 2;327:62-76
references.pmid: 25446327
references.citation: Mol Pharmacol. 2012 Jul;82(1):90-6
references.pmid: 22498659
references.citation: Cancer Lett. 2008 Apr 8;262(1):28-36
references.pmid: 18164123
references.citation: Inflammation. 2016 Feb;39(1):434-46
references.pmid: 26433578
references.citation: Ann N Y Acad Sci. 2000;921:92-102
references.pmid: 11193883
references.citation: Inhal Toxicol. 2000 Jan;12 Suppl 3:317-26
references.pmid: 26368631
references.citation: Sci China Life Sci. 2015 Sep;58(9):867-75
references.pmid: 26354506
references.citation: J Exp Med. 1994 Sep 1;180(3):945-58
references.pmid: 8064242