Impact of probiotics on toll-like receptor 4 expression in an experimental model of ulcerative colitis

Abstract

Toll-like receptors (TLRs) are key components of the innate immune system which trigger antimicrobial host defense responses. This study aimed to investigate the impact of probiotics (Lactobacillus, Bifiidobacterium) on the expression of TLR4 and tumor necrosis factor-alpha (TNF-α) in the colon mucosa of rat experimental ulcerative colitis model induced by trinitrobenzene sulfonic acid (TNBS)/ethanol and immune complexes. The gross and histological changes of the colonic mucosa were observed and assessed by the means-standard deviation and independent samples t-test. The protein expression levels of TLR4 and TNF-α were detected by using immunohistochemistry and Western blotting, respectively. It was revealed that there was visible infiltration of inflammatory cells, formation of crypt abscess, and the reduction of goblet cells in the colon tissue of experimental models. As compared with the control group, the levels of TLR4 and TNF-α protein were significantly increased in the model group (P<0.01 for both). No significant difference was found in the expression of TLR4 and TNF-α between the two-week probiotics treatment group and the model group (P>0.05), whereas significant reductions were shown in rats which were treated with probiotics for four weeks as compared with the model group (P<0.01). There was no significant difference between two probiotics-treated groups. Our results implied that probiotics were likely to play a key role in protecting ulcerative colitis by reducing the inflammatory factor TNF-α expression through inhibiting the TLR4 expression in the colon tissue of experimental models.

Keywords

ulcerative colitis / animal model / Toll-like receptor 4 / tumor necrosis factor-α / trinitrobenzene sulfonic acid

References

[1] SartorRB. Microbial influences in inflammatory bowel diseases. Gastroenterology, 2008, 134(2): 577-594

[2] XavierRJ, PodolskyDK. Unravel1ing the pathogenesis of inflammatory bowel disease. Nature, 2007, 448(7152): 427-434

[3] XuSY, BianRL, ChenX. . Experimental methodology of pharmacology, 1991, Beijing, People’s Medical Publishing House, 11

[4] CooperHS, MurthySN, ShahRS, et al.. Clinic pathologic study of dextran sulfate sodium experim ental murine colitis. Lab Invest, 1993, 69(2): 238-249

[5] KaserA, ZeissigS, BlumbergRS. Inflammatory bowel disease. Annu Rev Immunol, 2010, 28(2): 562-573

[6] SartorRB. Mechanisms of disease: pathogenesis of crohn’s disease and ulcerative colitis. Nat Clin Pract Gatroenterol Hepatol, 2006, 3(7): 390-406

[7] BlamME, SteinRB, LichtensteinGR. Integrating antitumor necrosis factor therapy in inflammatory bowel disease: current and future perspectives. Am J Gastroenterol, 2001, 96(7): 1977-1997

[8] KatoK, MizunoS, UmesakiY, et al.. Randomized placebo-controlled trial assessing the effect of bifidobacteria.-fermented milk on active ulcerative colitis. Aliment Pharmacol Ther, 2004, 20(10): 1133-1141

[9] RiouxK, FedorakR. Probiotics in the treatment of inflammatory bowel disease. J Clin Gastroenterol, 2006, 40(3): 260-263

[10] KuhbacherT, OttSJ, HelwigU, et al.. Bacterial and fungal microbiota in relation to probiotic therapy (VSL#3) in pouchitis. Gut, 2006, 55(6): 833-841

[11] RachmilewitzD, KarmeliF, ShteingartS, et al.. Immunostimulatory oligonuc1eotides inhibit colonic proinflammatory cytokine production in ulcerative colitis. Inflamm Bowel Dis, 2006, 12(5): 339-345

[12] SiddiqueI, KhanI. Mechanism of regulation of Na-H exchanger in inflammatory bowel disease: Role of TLR4 signaling mechanism. Dig Dis Sci, 2011, 56(6): 1656-1662

[13] RutellaS, LocatelliF. Intestinal dendritic cells in the pathogenesis of inflammatory bowel disease. World J Gastroenterol, 2011, 17(33): 3761-3775

[14] ManolakisAC, KapsoritakisAN, KapsoritakiA, et al.. Readressing the role of Toll-like receptor-4 alleles in inflammatory bowel disease: colitis, smoking, and seroreactivity. Dig Dis Sci, 2013, 58(2): 371-380