Role of p38 Mitogen-activated Protein Kinase Pathway in Pathogenesis of Ulcerative Colitis

HE Fu-qian, ZOU Yu-pei, HUANG Xiao-li, GAO Feng-jiao, PENG Lan, GAN Hua-tian

Abstract

To elucidate the role of p38 mitogen-activated protein kinase (p38MAPK) in the pathogenesis of ulcerative colitis (UC) and DSS-induced colitis in mice. Methods ① 27 Balb/c mice were divided randomly into three groups:DSS-induced colitis group, normal control group and SB203580 treatment group. In DSS-induced colitis group, mice were feed with 5%DSS solution. In SB203580 treatment group, mice were feed with 5%DSS solution for 72 hours, then treated with intraperitoneal injection of SB203580 (1 mg/kg) once daily. Disease activity index (DAI) was record to evaluate the severity of colitis. The mice were executed after 7 days. The levels of TNF-α and IL-1β were measured by ELISA. ② A total of 54 cases were included in the study. 36 cases were patients with active ulcerative colitis, 18 cases were normal mucosa from 18 colon cancer cases served as control. Effects of SB203580 (a selective p38MAPK inhibitor) on expression of TNF-α and IL-1β in intestinal mucosal biopsy specimens from patients with ulcerative colitis were determined on condition of tissue culture. Results ① The DAI scores, the levels of TNF-α and IL-1β in SB203580 group were lower significantly compared with DSS group (P<0.05), and were increased significantly compared with normal control group (P<0.05). ② The levels of TNF-α and IL-1β in intestinal mucosal biopsy specimens in SB203580 treatment group were lower significantly than those in UC group (P<0.05). Conclusion SB203580 can inhibit p38MAPK signal transduction pathway, then reduce the expression of pro-inflammatory cytokine TNF-α and IL-1β.

 

Keywords: p38 mitogen-activated protein kinase, SB2035 80, Ulcerative colitis, DSS-induced colitis, Tumor necrosis factor-α, Interleukin-1β

 

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References


Papadakis KA, Targan SR. Role of cytokines in the pathogenesis of inflammatory bowel disease. Annu Rev Med, 2000;51:289-298.

MurchSH, Braegger CP. Walker-Smith JA, et al. Location of tumor necrosis factor alpha by immunohistochemistry in chronic inflammatory bowel disease. Gut, 1993;34(12); 1705-1709.

Schreiber S, Nikolaus S, Hampe J , et al. Tumor necrosis factor alpha and interleukin lbeta in relapse of Crohn ’ s disease. Lancet, 1999;353(9151 ):459-461.

Zarubin T, Jiahuai H. Activation and signaling of the p38 MAK kinase pathway. Cell Res,2005 ; 15(1); 11-18.

Cooper HS, Murthy SN, Shah RS, et al. Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest, 1993;69(2):238-249.

Hollenbach E, Neumann M, Vieth M, et al. Inhibition of P38 MAP kinase-and RICK/NF-kappaB-signaling suppresses inflammatory bowel disease. FASEB J, 2004; 18 ( 13 ); 1550- 1552.encephalopathy. J Perinat Neonatal Nurs,2009 ;23(1) :59-68.

Catania MA. Marciano МС, Parisi A, et al. Erythropoietin prevents cognition impairment induced by transient brain ischemia in gerbils. Eur J Pharmacol.2002;437(3) : 147-150.

Celik M, Gokmen N, Erbayraktar S, et al. Erythropoietin prevents motor neuron apoptosis and neurologic disability in experimental spinal cord ischemic injury. Proc Natl Acad Sci U S A.2002;99(4):2258-2263.

Tanaka M, Natori M. Ishimoto H, et al. Experimental growth retardation produced by transient period of uteroplacental ischemia in pregnant Sprague-Dawley rats. Am J Obstet Gynecol, 1994 ; 171 (5); 1231-1234.

Johnston MV, Treseller WH, Ishida A, et al. Neurobiology of hypoxic-ischemic injury in the developing brain. Pediatr Res, 2001;49(6);735-741.

Kumral A, Ozer E, Yilmaz O, et al. Neuroprotective effect of erythropoietin on hypoxic-ischemic brain injury in neonatal rats. Biol Neonate,2003;83(3):224-228.

Brines ML, Ghezzi P, Keenan S, et al. Erythropoietin crosses the blood-brain barrier to protect against experimental brain injury. Proc Natl Acad Sci U S A,2000;97( 19): 10526-10531.

Bernal F, Saura J, Ojuel J, et al. Differential vulnerability of hippocampus, basal ganglia, and prefrontal cortex to long-term NMDA excitotoxicity. Exp Neurol,2000; 161(2):686-695.

Fan TJ, Han LH, Cong RS, et al. Caspase family proteases and apoptosis. Acta Biochim Biophys Sin (Shanghai) ,2005;37 (11);719-727.

Ferrer I, Friguls B, Dalfo E, et al. Caspase-dependent and caspase- independent signaling of apoptosis in the penumbra following middle cerebrsl artery occlusion in the adult rat. Neuropathol Appl Neurobiol. 2003 ; 29(5);472-481.

Murano M, Maemura К, Hirata I. et al. Therapeutic effect of intracolonically administered nuclear factor kappa В ( P65 ) antisense oligonucleotide on mouse dextran sulphate sodium (DSS)-induced colitis. Clin Exp Immunol, 2000; 120( 1); 51-58. Eastwood GL, Trier JS. Organ culture of human rectal mucosa. Gastroenterology, 1973;64(3) ;375-382.

Waetzig GH, Seegert D. Rosenstiel P, et al. P38 mitogen- activated protein kinase is activated and linked to TNF-a signaling in inflammatory bowel disease. J Immunol. 2002; 168 (10):5342-5351.

Podolsky DK. Inflammation bowel disease. N Engl Med,2002; 347(6);417-429.

Sawa Y, Oshitani N, Adachi K, et al. Comprehensive analysis of intestinal cytokine messenger RNA profile by real-time quantitative po lymerase chain reaction in patients with inflammatory bowel disease. Int J Mol Med, 2003; 2( 11); 175- 179.

Wu HG, Liu HR, Zhao С, et al. Study on differentially expressed genes of ulcerative colitis in the rat treated by herbs- partitioned moxibustion. Zhongguo Zhen Jiu,2005;25(5): 359- 365.

Stevens C, Walz G, Singaram C, et al. Tumor necrosis facto- a, interleukin-1|3 and interleukin 6 expression in inflammatory bowel disease. Dig Dis Sci, 1992;37(6):818-826.

Pullamn WE, Elsburg S, Kobayashi M, et al. Enhanced mucosal cytokine production in inflammatory bowel disease. Gastroenterology, 1992; 102 ;529-537.

Neurath M« Meyer КН. Protective and pathogenic roles of cytokines in inflammatory bowel disease. J Invest Med. 1996; 44:516-521.

Paul Rutgeerts MD, William J, Sandborn MD, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med .2005; 353( 23): 2462-2476.

Robinson MJ, Cobb MH. Mitegen-activated protein kinase pathways. Curr Opin Cell Biol. 1997;9(2); 180-186.

Hommes DW, Peppelenbosch MP. Van Deventer SJ. Mitogen activated protein ( MAP) kinase signal transduction pathways and novel anti-inflammatory targets. Gut, 2003; 52 ( 1 ) : 144- 151.

Badeger AM. Bradbeer JN, Votta B. et al. Pharmacological profile of SB203580, a selective inhibitor of cytokine suppressive binding protein/P38 kinase, in animal models of arthritis, bone resorption, endotoxin shock and immune function. J Pharmacol Exp Ther. 1996 ; 279(3) : 1453-1461.

Denham W, Yang J. Wang H. et al. Inhibition of P38 mitogen activate kinase attenuates the severity of pancreatitis-induced adult respiratory distress syndrome. Crit Care Med, 2000; 28 (7):2567-2572.

WaetzigGH, Seegert D. Rosenstiel P. et al. p38 mitogen- activated protein kinase is activated and linked to TNF-alpha signaling in inflammatory bowel disease. J Immunol,2002; 168 (10):5342-5351.


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