Effect of folate deficiency on experimental colitis in mice induced by dextran sodium sulfate / 中华消化杂志

ABSTRACT

Objective To investigate whether folate deficiency cause high expression level of interferon gamma (IFN-γ) resulted from IFN-γ gene ( IFNG) hypomethylation and then promote the pathogenesis and development of ulcerative colitis (UC ) in a dextran sulfate sodium (DSS )-induced experimental colitis model in mice .Methods A total of 24 female BALB/c mice were divided into four groups ,six mice in each group , including folate deficient/DSS+ group , standard diet/DSS+ group , standard diet/DSS - group and folate deficient/DSS- group .At the beginning of the sixth week since fed , the mice of model groups were treated with 5% DSS to establish experimental colitis .By the end of the sixth week ,disease activity index (DAI) of colitis and histological changes were evaluated .The folate level of peripheral blood serum of mice were detected by enzyme-linked immunosorbent assay (ELISA ) . The expression of IFN-γ in colonic mucosa of mice was examined by immunohistochemistry . The methylation level of CpG island in the promoter region of IFNG was determined by methylation specific polymerase chain reaction (MSP) .The t test was used for measurement data .Chi square test was performed for comparison between groups of count data . Spearman correlation analysis was used for correlation analysis .Results The folate levels of peripheral blood serum of folate deficiency/DSS+ group and folate deficiency/DSS- group ((2 .70 ± 0 .19) and (2 .80 ± 0 .25)μg/L) were significantly lower than those of standard diet/DSS+ group and standard diet/DSS- group ((13 .62 ± 0 .38 ) and (13 .52 ± 0 .77)μg/L ,t= -63 .33、32 .27 ,both P< 0 .05) ,resepectively .The expression of IFN-γ in colonic mucosa of folate deficiency/DSS+ group and standard diet/DSS+ group were significantly higher than those of folate deficiency/DSS- group and standard diet/DSS- group (χ2 = 22 .18 ,P< 0 .05 ) . And the expression of IFN-γ in colonic mucosa of folate deficiency/DSS+ group was also higher than that of standard diet/DSS+ group (χ2 = 12 .00 ,P< 0 .05) .The expression level of IFN-γ of folate deficiency/DSS+ group and standard diet/DSS+ group was positively correlated with (r=0 .998、0 .953 ,both P<0 .01) .The folate levels of peripheral blood serum of folate deficiency/DSS+ group was negatively correlated with IFN-γexpression level and DAI (r= -0 .880 and -0 .926 ,both P<0 .05) .No abnormal methylation was detected in IFNG promoter CpG island in colonic mucosa tissues of mice of each group . Conclusion In the mice model of DSS induced acute experimental colitis ,folate deficiency may increace the expression of inflammatory factor IFN-γand enhance the inflammation activity of colonic mucosa .