The anti-inflammatory effects of a high-frequency oligodeoxynucleotide from the genomic DNA of Lactobacillus casei.

Abstract

Genomic DNA has been identified as an anti-inflammatory component of Lactobacillus species, the effects of which are mediated through toll-like receptor (TLR) 9. In this study, we identified 14 novel anti-inflammatory oligodeoxynucleotide (ODN) from the genomic DNA of Lactobacillus casei by measuring their effects on the secretion of interleukin (IL)-8 (CXCL8) in the human epithelial colorectal adenocarcinoma cell line Caco-2 cells. The ODN TTTTGCCG strongly decreased IL-8 secretion. In the genomic DNA of Lactobacillus species, the frequency of TTTTGCCG was highest in the genomic DNA of L. casei and similar among strains of L. casei. Decreases in inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 expressions in macrophage-like differentiated THP-1 cells confirmed the anti-inflammatory effect of TTTTGCCG. Furthermore, oral administration of TTTTGCCG ameliorated dextran sodium sulfate (DSS)-induced murine colitis and DSS-induced increased expression of inflammatory factor mRNAs, such as macrophage inflammatory protein (MIP)-2 (CXCL2), iNOS, and COX-2. The anti-inflammatory effect of TTTTGCCG was mainly regulated by an increase in heat shock protein (Hsp) 70 expression in the epithelium. TLR9 and Hsp90 may primarily mediate the anti-inflammatory effect of TTTTGCCG on Hsp70 signaling.