Lactobacillus plantarum lipoteichoic acid down-regulated Shigella flexneri peptidoglycan-induced inflammation.
Bacterial peptidoglycans (PGNs) are recognized by the host's innate immune system. This process is mediated by the NOD/CARD family of proteins, which induces inflammation by activating nuclear factor (NF)-κB. Excessive activation of monocytes by Shigella flexneri PGN (flexPGN) leads to serious inflammatory diseases such as intestinal bowel diseases (IBD) and Crohn's disease. In this study, we examined whether Lactobacillus plantarum lipoteichoic acid (pLTA) could attenuate the pro-inflammatory signaling induced by flexPGN in human monocytic THP-1 cells. Compared to control THP-1 cells, pLTA-tolerant cells showed a significant reduction in TNF-α and IL-1β production in response to flexPGN. We also examined the inhibition of NF-κB and the activation of mitogen-activated protein kinase (MAPK) in pLTA-tolerant cells. We found that the expression of NOD2 in pLTA-tolerant cells was down-regulated at the mRNA and protein levels, suggesting that pLTA is a potent modulator of the pro-inflammatory NOD2-related signaling pathways induced by flexPGN. Together, these data indicate that pLTA induces cross-tolerance against flexPGN. Notably, these effects are related not only to IL-1 signaling, which is known to play a role in LPS tolerance, but also to NOD-Rick signaling. This study provides insight into how commensal microflora may contribute to homeostasis of the host intestinal tract.
School of Biotechnology and Institute of Life Science and Resources, Kyung Hee University, Yongin 449-701, South Korea.
Han Geun
HG
Kim
Seung Yeon
SY
Lee
Na Ra
NR
Kim
Hea Young
HY
Lee
Mi Yeon
MY
Ko
Bong Jun
BJ
Jung
Chul Min
CM
Kim
Jung Min
JM
Lee
Jong Hwan
JH
Park
Seung Hyun
SH
Han
Dae Kyun
DK
Chung
D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D015536:Down-Regulation / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism / Q000494:pharmacology; D007422:Intestines / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D048191:Lactiplantibacillus plantarum / Q000737:chemistry*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism; D010457:Peptidoglycan / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012763:Shigella flexneri / Q000737:chemistry*; D013682:Teichoic Acids / Q000494:pharmacology*; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D010457:Peptidoglycan; D012333:RNA, Messenger; C495342:TLR2 protein, human; D013682:Teichoic Acids; D051195:Toll-Like Receptor 2; C009900:lipoteichoic acid; D020928:Mitogen-Activated Protein Kinases