HOME | LOG IN | SIGN UP

Cytotoxic effect of triptolide on LPS-treated macrophages through sustained phosphorylation of p38 MAP kinase and apoptosis

Kiyoko Kohama, Atsushi Koike, Fumio Amano

Abstract


Triptolide induced the death of cells of lipopolysaccharide (LPS)- treated macrophage-like cell line J774.1/JA-4 cells through apoptosis but not through activation during incubation at 37oC for 4 h. This phenomenon was dependent on the dose and the time of addition of triptolide; and prior or simultaneous addition to LPS was needed, suggesting mal-regulation of LPS-signaling cascades. LPS rapidly induced phosphorylation of p38 MAP kinase, JNK and Erk1/2 within 15 min of its addition, and then dephosphorylation of them followed by 60 min. However, the addition of triptolide, but not endothall, inhibited this dephosphorylation of phospho-p38 and phosphor-JNK in these cells, suggesting that MKP-1 was involved in the dephosphorylation of these phosphoproteins. Triptolide inhibited the synthesis of MKP-1 mRNA and protein induced by LPS. Compared with our previous studies, where a protein synthesis inhibitor, cycloheximide (CHX), induced rapid apoptotic cell death in LPS-treated macrophages through sustained phosphorylation of p38, triptolide seemed to induce cell death of LPS-treated macrophages by inhibition of MKP-1 induction.

Keywords


macrophage cell death; triptolide; lipopolysaccharide (LPS); p38 MAP kinase; phosphorylation, apoptosis, MKP-1

Full Text:

References


Gutknecht MF, Bouton AH. Functional significance of mononuclear phagocyte populations generated through adult hematopoiesis. J. Leukocyte Biol. 96 (6) 2014, 969-80

Alexander P, Evans R. Endotoxin and double-stranded RNA render macrophage cytotoxic. Nature New Biol. 232 (29) 1971, 76-78.

Klimp AH, de Vries EGE, Scherphof GL, Daemen T. A potential role of macrophage activation in the treatment of cancer. Critical Reviews in Oncology/Hematology 44 (2) 2002, 143–161

Amano F, Karahashi H. A cytotoxic effect of lipopolysaccharide (LPS) on a macrophage-like cell line, J774.1, in the presence of cycloheximide. J. Endotoxin Res., 3 (5) 1996, 415–423.

Karahashi H, Amano F. Apoptotic changes preceding necrosis in lipopolysaccharide-treated macrophages in the presence of cycloheximide. Exp. Cell Res., 241 (2) 1998, 373–383.

Karahashi H, Amano F. Changes of caspase activities involved in apoptosis of a macrophage-like cell line J774.1/JA-4 treated with lipopolysaccharide (LPS) and cycloheximide. Biol.Pharm.Bull., 23 (2) 2000, 140-144.

Karahashi H, Nagata K, Ishii K, Amano F. A selective inhibitor of p38 MAP kinase, SB202190, induced apoptotic cell death of a lipopolysaccharide-treated macrophage-like cell line, J774.1. Biochim. Biophys. Acta., 1502 (2) 2000, 207-223.

Karahashi H, Amano F. Endotoxin-tolerance to the cytotoxicity toward a macrophage-like cell line, J774.1, induced by lipopolysaccharaide and cycloheximide: role of p38 MAPK in induction of the cytotoxicity. Biol.Pharm.Bull. 26 (9) 2003, 1249-1259.

Karahashi H, Amano F. LPS-induced signals in activation of a caspase-3-like protease, a key enzyme regulating cell damage into a macrophage-like cell line, J774.1, in the presence of cycloheximide. J. Leukocyte Biol., 66 (4) 1999, 689-696.

Kupchan SM, Court WA, Dailey RG, Gilmore CJ, Bryan RF. Triptolide and tripdiolide, novel antileukemic diterpenoid triepoxides from Tripterygium wilfordii. J Am Chem Soc., 94 (20) 1972, 7194-7195.

Chen P, Li J, Barnes J, Kokkonen GC, Lee JC, Liu Y. Restraint of proinflammatory cytokine biosynthesis by mitogen-activated protein kinase phosphatase-1 in lipopolysaccharide-stimulated macrophages. J. Immunol., 169 (11) 2002, 6408-6416.

Wang J, Zhou J-Y, Zhang L, Wu GS. Involvement of MKP-1 and Bcl-2 in acquired cicplatin resistance in ovarian cancer cells. Cell Cycle, 8 (19) 2009, 3191-3198.

Li Y-M, Mackintosh C, Casida J. Protein phosphatase 2A and its [3H]cantharidin/[3H]endothall thioanhydride binding site. Biochem. Pharmacol., 46(8) 1993, 1435-1443.

Amano F, Akamatsu Y. A lipopolysaccharide (LPS)-resistant mutant isolated from a macrophage-like cell line, J774.1, exhibits an altered activated-macrophage phenotype in response to LPS. Infect. Immun., 59 (6) 1991, 2166–2174.

Koike A, Minamiguchi I, Fujimori K, Amano F. Nitric oxide is an important regulator of heme oxygenase-1 expression in the lipopolysaccharide and interferon-gamma-treated murine macrophage-like cell line J774.1/JA-4. Biol. Pharm. Bull., 38 (1) 2015, 7–16.

Koike A, Shibano M, Mori H, Kohama K, Fujimori K, Amano F. Simultaneous addition of Shikonin and its derivatives with lipopolysaccharide induces rapid macrophage death. Biol. Pharm. Bull., 39 (6) 2016, 969–976.

Karahashi H, Amano F. Lipopolysaccharide (LPS)-induced cell death of C3H mouse peritoneal macrophages in the presence of cycloheximide: different susceptibilities of C3H/HeN and C3H/HeJ mice macrophages. J. Endotoxin Res., 6 (1) 2000, 33–39.

Amano F, Tsukabe S, Teshima R, Waku K, Kohama K. Characterization of macrophage mutants established by their resistance to LPS and cycloheximide-induced apopotic cell death. Advances in Bioscience and Biotechnology, 3 2012, 770–781.

Karahashi H, Amano F. Structure-activity relationships of lipopolysaccharide (LPS) in tumor necrosis factor- (TNF-) production and induction of macrophage cell death in the presence of cycloheximide (CHX) in a murine macrophage-like cell line, J774.1. Biol. Pharm. Bull., 21 (10) 1998, 1102–1105.

Zhao Q, Shepherd EG, Manson ME, Nelin LD, Sorokin A, Liu Y. The role of mitogen-activated protein kinase phosphatase-1 in the response of alveolar macrophages to lipopolysaccharide: attenuation of proinflammatory cytokine biosynthesis via feedback control of p38. J. Biol. Chem., 280 (9) 2005, 8101-8108.

Matta R, Wang X, Ge H, Ray W, Nelin LD, Liu Y. Triptolide induces anti-inflammatory cellular responses. Am. J. Transl. Res., 1(3) 2009, 267-82.

Yang F, Bai XJ, Hu D, Li ZF, Liu KJ. Effect of triptolide on secretion of inflammatory cellular factors TNF-α and IL-8 in peritoneal macrophages of mice activated by lipopolysaccharide. World J. Emerg. Med., 1 (1) 2010, 70-4.

Zhou R, Zheng SX, Tang W, He PL, Li XY, Yang YF, Li YC, Geng JG, Zuo JP. Inhibition of inducible nitric-oxide synthase expression by (5R)-5-hydroxytriptolide in interferon-gamma- and bacterial lipopolysaccharide-stimulated macrophages. J. Pharmacol .Exp. Ther., 316 (1) 2006, 121-8.

Patel BS, Co WS, Donat C, Wang M, Che W, Prabhala P, Schuster F, Schulz V, Martin JL, Ammit AJ. Repression of breast cancer cell growth by proteasome inhibitors in vitro: impact of mitogen-activated protein kinase phosphatase 1.Cancer Biol. Ther., 16(5) 2015, 780-9.

Zhou Y, Ling EA, Dheen ST. Dexamethasone suppresses monocyte chemoattractant protein-1 production via mitogen activated protein kinase phosphatase-1 dependent inhibition of Jun N-terminal kinase and p38 mitogen-activated protein kinase in activated rat microglia. J. Neurochem., 102(3) 2007, 667-78.

Kurata S. Selective activation of p38 MAPK cascade and mitotic arrest caused by low level oxidative stress. J Biol Chem., 275 (31) 2000, 23413-6.

Krifka S, Petzel C, Hiller KA, Frank EM, Bosl C, Spagnuolo G, Reichl FX, Schmalz G, Schweikl H. Resin monomer-induced differential activation of MAP kinases and apoptosis in mouse macrophages and human pulp cells. Biomaterials., 31 (11) 2010, 2964-75.

Lu Y, Zhang Y, Li L, Feng X, Ding S, Zheng W, Li J, Shen P. TAB1: a target of triptolide in macrophages. Chem. Biol., 21 (2) 2014, 246-56.

Wang W, Zhou G, Hu MC, Yao Z, Tan TH. Activation of the hematopoietic progenitor kinase-1 (HPK1)-dependent, stress-activated c-Jun N-terminal kinase (JNK) pathway by transforming growth factor beta (TGF-beta)-activated kinase (TAK1), a kinase mediator of TGF beta signal transduction. J. Biol. Chem., 272 (36) 1997, 22771-5.

Bao X, Cui J, Wu Y, Han X, Gao C, Hua Z, Shen P. The roles of endogenous reactive oxygen species and nitric oxide in triptolide-induced apoptotic cell death in macrophages. J. Mol. Med. (Berl)., 85 (1) 2007, 85-98.

Wu Y, Cui J, Bao X, Chan S, Young DO, Liu D, Shen P. Triptolide attenuates oxidative stress, NF-kappaB activation and multiple cytokine gene expression in murine peritoneal macrophage. Int. J. Mol. Med., 17 (1) 2006, 141-50.

Choi YJ, Kim TG, Kim YH, Lee SH, Kwon YK, Suh SI, Park JW, Kwon TK. Immunosuppressant PG490 (triptolide) induces apoptosis through the activation of caspase-3 and down-regulation of XIAP in U937 cells. Biochem. Pharmacol., 66 (2) 2003, 273-80.




DOI: http://dx.doi.org/10.18103/ibr.v1i2.1399

Refbacks

  • There are currently no refbacks.