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

• Published in: International immunopharmacology 2014-11, Vol.23 (1), p.139-147
• Main Authors: Hiramatsu, Yukihiro, Satho, Tomomitsu, Hyakutake, Mika, Irie, Keiichi, Mishima, Kenichi, Miake, Fumio, Kashige, Nobuhiro
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Anti-inflammatory effect; Caco-2 Cells; Colitis - chemically induced; Colitis - therapy; Cyclooxygenase 2 - metabolism; Dextran Sulfate - metabolism; DNA, Bacterial - administration & dosage; DNA, Bacterial - genetics; Epithelial Cells - physiology; Heat shock protein; HSP72 Heat-Shock Proteins - genetics; HSP72 Heat-Shock Proteins - metabolism; Humans; Interleukin-8 - metabolism; Lactobacillus casei; Lactobacillus casei - immunology; Macrophages - physiology; Male; Mice; Mice, Inbred C57BL; Nitric Oxide Synthase Type II - metabolism; Oligodeoxynucleotide; Oligodeoxyribonucleotides - administration & dosage; Signal Transduction - genetics; Toll-like receptor 9; Toll-Like Receptor 9 - metabolism
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2014.08.013

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. •TTTTGCCG is enriched in the genomic DNA of Lactobacillus casei.•TTTTGCCG show strong anti-inflammatory effects in epithelial cells and macrophage.•Oral administration of TTTTGCCG ameliorate DSS-induced murine colitis.•TLR9 and Hsp90 primarily mediate the anti-inflammatory effects of TTTTGCCG.•TTTTGCCG exerts the anti-inflammatory effects through Hsp70 signaling.