Učinak azitromicina na ekspresiju TLR-4, TNFalfa i TGFbeta u crijevnoj sluznici miševa s eksperimentalnim kolitisom The effect of azithromycin on TLR-4, TNF alpha and TGF beta expression in bowel mucosa in a murine model of experimental colitis

摘要

Changes in expression of pro- and anti-inflammatory cytokines and membrane receptors areuddocumented patients with IBD. The aim of this study was to investigate the effect ofudazithromycin on expression of TLR-4, TNFalpha i TGFbeta in bowel mucosa in murine modeludof experimental colitis induced by enema 2, 4 –dinitrofluorobenzen. Immunohistochemistryudwas performed from paraffin embedded murine intestinal tissue for TLR-4, TNFalpha iudTGFbeta. Experimental groups of animals were treated with azithromycin, metronidazole orudmethylprednisolone for five days, respectively and the control group was the group of healthyudmice and group of mice with experimental colitis. Results of this study showed the changesudin expression of pro- and anti-inflammatory cytokines (TLR-4, TNFalpha i TGFbeta) inudmanipulation of experimental colitis induced by DNFB. The expected differences inudexpression markers: significantly increased expression of TNFα i TLR4, and significantllyuddecreased expression of TGFβ in bowel mucosa in a murine model of experimental colitisudcompared to bowel mucosa of healthy mice. The results of this study documented theuddifferences in expression of observed markers; smaller expression of TNFα i TLR4 in boweludmucosa treated with methilprednizolone and azithromycin and larger expression of TGFβ inudbowel mucosa of mice with experimental colitis treted with methilprednizolone, azithromycinudand metronidazol. In murine bowel mucosa treated with metronidazol no differences wereudnoted compared with group with experimental colitis. Metronidazol showed weakudantiinflammatory effect compared to methilprednizolone and azithromycin. The effect ofudtreatment on expression of markers documented that the effect of metronidazole on theudreduction of TNF and TLR4 expression on mononuclear cells of submucosa was significantlyudweaker than the effect of methylprednisolone and azithromycin. There was no significantuddifference between methylprednisolone and the effect of azithromycin on the reduction ofudTNF and TLR4 expression. There was no significant difference between the effect ofudmethylprednisolone, azithromycin and metronidazole on expression of TGFβ. Theudantiinflammatory effect of azithromycin was not significantly different from the antiinflammatoryudeffect of methylprednisolone. According to the results azithromycin shows theudcorresponding anti-inflammatory effect which manifested itself in a significant reduction ofudexpression of TNFα and TLR4 with potential clinical implications, regarding the activityudpatterns of inflammation perpetuation and the period of the biological course of inflammatoryudbowel disease in humans.