Association between -defensin 5 and the expression and function of P-glycoprotein in differentiated intestinal Caco-2 cells

alpha-Defensin 5 is known to be secreted by Paneth cells in the small intestine and plays an important role in eliminating pathogenic microorganisms. It has been reported that a decrease in alpha-defensin 5 level in the human small intestine is a risk of inflammatory bowel disease (IBD). Furthermore, P-glycoprotein (P-gp), a member of the ATP-binding cassette transporter superfamily, encoded by the ABCB1/MDR1 gene, plays an important role in the front line of host defense by protecting the gastrointestinal barrier from xenobiotic accumulation and may contribute to the development and persistence of IBD. Therefore, we examined the relationship between alpha-defensin 5 and the expression and function of P-gp using a human gastrointestinal model cell line (Caco-2). We found that MDR1 mRNA and P-gp protein level were increased in Caco-2 cells as well as alpha-defensin 5 secretion corresponded with the duration of cell culture. Exposure to alpha-defensin 5 peptide and recombinant tumor necrosis factor-alpha (TNF-alpha) significantly increased the expression and function P-gp. The mRNA levels of interleukin (IL)-8, IL-6, TNF-alpha, IL-1 beta, and IL-2 were also increased following exposure to TNF-alpha, similar to alpha-defensin 5 treatment. These results suggest that alpha-defensin 5 regulates P-gp expression and function by increasing TNF-alpha expression in Caco-2 cells.