The Role Of C-reactive Protein In Ulcerative Colitis

Background: C-reactive protein(CRP)is a typical acute phase protein.Its concentration increases rapidly in the blood after tissue injury or infection,and it is a nonspecific marker of inflammatory response.At the same time,CRP plays a key regulatory role in innate and acquired immunity,and is directly involved in the regulation of many chronic or acute inflammatory diseases.Ulcerative colitis(UC)is an inflammatory bowel disease,the incidence of which is increasing year by year worldwide,lasting for a long time and recurrent,seriously affecting the normal life of patients.It has been reported that the expression level of CRP is significantly correlated with the therapeutic effect of many drugs on UC,but whether CRP is directly involved in the regulation of UC is not well reported.The purpose of this study is to reveal the role of CRP in the UC mouse model and provide theoretical guidance for the future research and treatment of UC.Methods: Dextran sodium sulfate(DSS)was used to induce C57BL/6J WT wildtype and CRP complete knockout mice to construct a mouse model of UC.Phenotype(body weight,colon length and spleen weight)and a series of physiological and biochemical indicators(disease activity index,colon histopathology,inflammatory factor expression,intestinal mucous barrier changes)of mice were determined.The effects of CRP on UC mice were evaluated and confirmed by adding CRP and measuring phenotypic changes in WT wild-type UC mice.The effects of CRP on UC mice were studied at the whole,tissue and molecular levels to further infer whether CRP is directly involved in UC process and its possible mechanism.Rseults:(1)By phenotypic and histopathological evaluation,it was found that UC could be induced in mice by oral administration of 2% DSS aqueous solution for about one week,and a mouse model of UC was successfully constructed(all p<0.001);(2)Compared with WT wild-type UC mice,knockdown of CRP had no significant effect on the phenotype(body weight,colon length and spleen weight),DAI score,inflammatory factor expression,mucus layer-associated.There was no significant effect on protein secretion and mucus layer thickness(all p>0.05),and only one result in four experiments analyzing the degree of inflammation in colonic tissues by HE staining showed that knockdown of CRP could promote colonic injury in UC mice(p<0.05),and similarly only one result in PAS staining showed that the number of cupped cells in UC mice was significantly reduced after knockdown of CRP(p<0.01);(3)Knockdown of CRP had no significant effect on UC mice,probably because CRP is at a lower expression level in mice and is only 2-fold increased in the acute phase,whereas CRP is upregulated 100-500-fold in human acute enteritis,which may predict that the mediation of CRP on UC in human depends on a higher concentration of action,so we added high concentrations of CRP in wild-type mice to bring plasma CRP in mice reached human acute phase levels.The addition of CRP to WT wild-type UC mice showed no significant effect on the phenotype(body weight,colon length and spleen weight)(p>0.05);(4)Considering that the effect of CRP might be masked by the effect of flora,we tried antibiotic treatment to exclude the interference of intestinal flora,and the results showed that even without the interference of intestinal flora,WT wild-type and The phenotypes(body weight,colon length and spleen weight)of CRP complete knockout UC mice were not significantly different(all p > 0.05);(5)the survival rate of CRP complete knockout mice induced by 5% high concentration of DSS was not significantly different from that of WT wild-type mice.Conclusions: Although blood CRP levels are significantly associated with UC recovery,our study suggests that CRP does not appear to be a direct mediator of UC disease,but rather that acute enteritis leads to increased expression of inflammatory factors that promote liver secretion of CRP.Our results suggest that CRP may only be a concomitant product downstream of UC disease,without significant proinflammatory or anti-inflammatory effects.But from an evolutionary point of view,nothing should be superfluous,and given the huge differences between mice and humans,the exact function of CRP in humans needs further study.