Browse > Article
http://dx.doi.org/10.5483/BMBRep.2016.49.3.271

Crotamine stimulates phagocytic activity by inducing nitric oxide and TNF-α via p38 and NFκ-B signaling in RAW 264.7 macrophages  

Lee, Kyung Jin (Department of Convergence Medicine, Asan Institute for Life Sciences)
Kim, Yun Kyu (Department of Convergence Medicine, Asan Institute for Life Sciences)
Krupa, Martin (Department of Physiology and Bio-Medical Institute of Technology)
Nguyen, Anh Ngoc (Department of Physiology and Bio-Medical Institute of Technology)
Do, Bich Hang (Department of Physiology and Bio-Medical Institute of Technology)
Chung, Boram (Department of Physiology and Bio-Medical Institute of Technology)
Vu, Thi Thu Trang (Department of Physiology and Bio-Medical Institute of Technology)
Kim, Song Cheol (Department of Surgery, Division of Hepatobilopancreatic Surgery, University of Ulsan College of Medicine, Asan Medical Center)
Choe, Han (Department of Physiology and Bio-Medical Institute of Technology)
Publication Information
BMB Reports / v.49, no.3, 2016 , pp. 185-190 More about this Journal
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.
Keywords
Crotamine; Macrophage; Nitric oxide; p38; TNF-α;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Kerkis I, Hayashi MA, Prieto da Silva AR et al (2014) State of the art in the studies on crotamine, a cell penetrating peptide from South American rattlesnake. Biomed Res Int 2014, 675985   DOI
2 Kerkis I, Silva Fde S, Pereira A, Kerkis A and Radis- Baptista G (2010) Biological versatility of crotamine--a cationic peptide from the venom of a South American rattlesnake. Expert Opin Investig Drugs 19, 1515-1525   DOI
3 Vu TT, Jeong B, Yu J et al (2014) Soluble prokaryotic expression and purification of crotamine using an N-terminal maltose-binding protein tag. Toxicon 92, 157-165   DOI
4 Peigneur S, Orts DJ, Prieto da Silva AR et al (2012) Crotamine pharmacology revisited: novel insights based on the inhibition of KV channels. Mol Pharmacol 82, 90-96   DOI
5 Zhu H, Yan L, Gu J, Hao W and Cao J (2015) Kv1.3 channel blockade enhances the phagocytic function of RAW264.7 macrophages. Sci China Life Sci 58, 867-875   DOI
6 Sinder BP, Pettit AR and McCauley LK (2015) Macrophages: Their Emerging Roles in Bone. J Bone Miner Res [Epub ahead of print]
7 Natoli G, Costanzo A, Ianni A et al (1997) Activation of SAPK/JNK by TNF receptor 1 through a noncytotoxic TRAF2-dependent pathway. Science 275, 200-203   DOI
8 Rodriguez D, Silvera R, Carrio R et al (2013) Tumor microenvironment profoundly modifies functional status of macrophages: peritoneal and tumor-associated macrophages are two very different subpopulations. Cell Immunol 283, 51-60   DOI
9 Teng L, Fu H, Wang M, Deng C and Chen J (2015) Stimulation of RAW264.7 macrophages by sulfated Escherichia coli K5 capsular polysaccharide in vitro. Mol Med Rep 12, 5545-5553   DOI
10 Schins RP and Donaldson K (2000) Nuclear factor Kappa- B activation by particles and fibers. Inhal Toxicol 12 Suppl 3, 317-326   DOI
11 Calderon C, Huang ZH, Gage DA, Sotomayor EM and Lopez DM (1994) Isolation of a nitric oxide inhibitor from mammary tumor cells and its characterization as phosphatidyl serine. J Exp Med 180, 945-958   DOI
12 Farias-Eisner R, Sherman MP, Aeberhard E and Chaudhuri G (1994) Nitric oxide is an important mediator for tumoricidal activity in vivo. Proc Natl Acad Sci U S A 91, 9407-9411   DOI
13 Karin M and Greten FR (2005) NF-kappaB: linking inflammation and immunity to cancer development and progression. Nat Rev Immunol 5, 749-759   DOI
14 Jin X, Wang J, Xia ZM et al (2015) Anti-inflammatory and anti-oxidative activities of paeonol and its metabolites through blocking MAPK/ERK/p38 signaling pathway. Inflammation [Epub ahead of print]
15 Chang CC and Tseng KH (1978) Effect of crotamine, a toxin of South American rattlesnake venom, on the sodium channel of murine skeletal muscle. Br J Pharmacol 63, 551-559   DOI
16 Leceta J, Gomariz RP, Martinez C, Abad C, Ganea D and Delgado M (2000) Receptors and transcriptional factors involved in the anti-inflammatory activity of VIP and PACAP. Ann N Y Acad Sci 921, 92-102   DOI
17 Sato T, Shoji H and Koga N (2003) Endotoxin adsorption by polymyxin B immobilized fiber column in patients with systemic inflammatory response syndrome: the Japanese experience. Ther Apher Dial 7, 252-258   DOI
18 Han EH, Hwang YP, Lee KJ, Jeong TC and Jeong HG (2008) 1-Bromopropane induces macrophage activation via extracellular signal-regulated kinase 1/2 MAPK and NF-kappaB pathways. Cancer Lett 262, 28-36   DOI
19 Pereira A, Kerkis A, Hayashi MA et al (2011) Crotamine toxicity and efficacy in mouse models of melanoma. Expert Opin Investig Drugs 20, 1189-1200   DOI
20 Cavaillon JM (1994) Cytokines and macrophages. Biomed Pharmacother 48, 445-453   DOI
21 Hibbs JB Jr, Taintor RR and Vavrin Z (1987) Macrophage cytotoxicity: role for L-arginine deiminase and imino nitrogen oxidation to nitrite. Science 235, 473-476   DOI
22 Ghosh S, May MJ and Kopp EB (1998) NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. Annu Rev Immunol 16, 225-260   DOI
23 MacMicking J, Xie QW and Nathan C (1997) Nitric oxide and macrophage function. Annu Rev Immunol 15, 323-350   DOI
24 Escolano A, Martinez-Martinez S, Alfranca A et al (2014) Specific calcineurin targeting in macrophages confers resistance to inflammation via MKP-1 and p38. EMBO J 33, 1117-1133   DOI
25 Lee D, Bae J, Kim YK et al (2013) Inhibitory effects of berberine on lipopolysaccharide-induced inducible nitric oxide synthase and the high-mobility group box 1 release in macrophages. Biochem Biophys Res Commun 431, 506-511   DOI
26 Qin Y, Zhou ZW, Pan ST et al (2015) Graphene quantum dots induce apoptosis, autophagy, and inflammatory response via p38 mitogen-activated protein kinase and nuclear factor-kappaB mediated signaling pathways in activated THP-1 macrophages. Toxicology 327, 62-76   DOI
27 Arayan LT, Simborio HL, Reyes AW et al (2015) The effects of red ginseng saponin fraction-A (RGSF-A) on phagocytosis and intracellular signaling in Brucella abortus infected RAW 264.7 cells. FEMS Microbiol Lett 362, fnv070   DOI
28 Liu S, Tobias R, McClure S, Styba G, Shi Q and Jackowski G (1997) Removal of endotoxin from recombinant protein preparations. Clin Biochem 30, 455-463   DOI
29 Bae J, Lee D, Kim YK, Gil M, Lee JY and Lee KJ (2013) Berberine protects 6-hydroxydopamine-induced human dopaminergic neuronal cell death through the induction of heme oxygenase-1. Mol Cells 35, 151-157   DOI