Chitooligosaccharide elicits acute inflammatory cytokine response through AP-1 pathway in human intestinal epithelial-like (Caco-2) cells

Chitooligosaccharides (COSs) are bioactive carbohydrate derivatives that have numerous health benefits, including stimulation of the immune system. The objectives of this study were to evaluate the effect of chitooligosaccharide (COS) on expression of a specific panel of cytokine genes involved in inflammation and to delineate the signal transduction pathway underlying the COS mediated inflammatory response. Human intestinal epithelial-like (Caco-2) cells were treated with COS (5000-10,000Da) and expression of a panel of eighty-four cytokine genes was analyzed by quantitative real-time PCR. COS induced up-regulation of a total of 11 genes including CCL20 and IL8 and concurrent down-regulation of 10 genes including pro-inflammatory mediators CCL15, CCL25 and IL1B. To further establish the signal transduction pathway of COS mediated response in Caco-2 cells, two major inflammatory signal transduction pathways (NF-κB and AP-1) were investigated. COS had inhibitory effect (P<0.01) on TNF-α induced NF-κB binding activity while stimulatory effect (P<0.001) on AP-1 binding activity. COS also inhibited the expression of RELA (P<0.01) and IKBKB (P<0.01) genes of NF-κB pathway while stimulate the expression of JUN (P<0.05) gene of AP-1 pathway. In conclusion, COS elicits an acute inflammatory cytokine response in Caco-2 cells and hence it has the potential to stimulate the immune system in the gut epithelium.