Chemokine receptor-2 (CCR-2) is a trans-membrane cell surface receptor that plays a key role in inflammation site, where the immune cells secrete inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha). The blockade of CCR2 prevents murine experimental colitis by inhibiting the recruitment of inflammatory cells. In Crohn's disease, the intestine shows an increase in CCR-2 expression. Studies in our laboratory suggest that neutrophil migration across intestinal epithelial monolayers is ameliorated by the presence of the probiotic agent Lactobacillus GG (LGG). We hypothesize that intestinal epithelial CCR-2 plays an important role in the process of trans-epithelial migration of neutrophils, and that the probiotic agent LGG ameliorates neutrophil migration by down-regulation of CCR-2. Total RNA was extracted from the T-84 intestinal epithelial cells exposed to the probiotic Lactobacillus GG in the presence or absence of chemoattractant using the RNAeasy method. Ten micrograms of fragmented cRNA was hybridized onto a HG U133A 2.0 gene chips (Affymetrix). The scanned images were processed using Affymetrix Microarray Suite version 5.0 and analyzed using GeneSpring 7.3. Samples were run in triplicates and student paired t-tests were used to identify significant changes among experimental groups. The most significant change was seen in Chemokine receptor-2 gene (CCR-2), which increased 7.5 folds with neutrophil migration (0.14 ± 0.28 versus 1.08 ± 0.32, n = 3, P = 0.02). The probiotic reversed the up-regulation of CCR-2 by diminishing gene expression to 0.4 fold (1.08 ± 0.32 versus 0.38 ± 0.14, n = 3, P = 0.03). The results of this study suggest that up-regulation of CCR-2 gene occurs during intestinal trans-epithelial migration of neutrophils and that down-regulation occurs with the probiotic Lactobacillus GG. Inhibition of CCR-2 can be the mechanism by which lactobacilli inhibit the process of neutrophil migration across the intestinal epithelial cells thus reducing intestinal inflammation in this model of cryptitis.
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Michail et al. (2006) studied this question.