NOD1 and NOD2 stimulation triggers innate immune responses of human periodontal ligament cells

Abstract

Nod-like receptors (NLRs) are cytosolic sensors for microbial molecules. Nucleotide-binding oligomerization domain (NOD)1 and NOD2 recognize the peptidoglycan derivatives, meso-diaminopimelic acid (meso-DAP) and muramyl dipeptide (MDP), respectively, and trigger host innate immune responses. In the present study, we examined the function of NOD1 and NOD2 on innate immune responses in human periodontal ligament (PDL) cells. The gene expression of NOD1 and NOD2 was examined by RT-PCR. IL-6 and IL-8 production in culture supernatants was measured by ELISA. Western blot analysis was performed to determine the activation of NF-κB and MAPK in response to Tri-DAP and MDP. The genes of NOD1 and NOD2 appeared to be expressed in PDL cells. Although the levels of NOD2 expression were weak in intact cells, MDP stimulation increased the gene expression of NOD2 in PDL cells. Tri-DAP and MDP led to the production of IL-6 and IL-8 and the activation of NF-κB and MAPK in PDL cells. Toll-like receptor (TLR) stimulation led to increased gene expression of NOD1 and NOD2 in PDL cells. Pam3CSK4 (a TLR2 agonist) and IFN-γ synergized with Tri-DAP and MDP to produce IL-8 and IL-6 in PDL cells. Our results indicate that NOD1 and NOD2 are functionally expressed in human PDL cells and can trigger innate immune responses.

Repeated handling compromises the immune suppression and improves the disease resistance in overwintering channel catfish (Ictalurus punctatus)

“…The present results were supported by that the enhanced IL8 mRNA expression was markedly suppressed in NOD2-and NOD1-silenced cells and the combinatory dual signaling through extracellular TLRs and intracellular NODs might lead to the synergistic activation of innate immune responses in host cells [24]. Toll-like receptor (TLR) stimulation has been reported to lead to increased gene expression of NOD1 and NOD2 in human periodontal ligament cells [25]. TLR2-TLR4 double-deficient mice are susceptible to Salmonella typhimurium, a Gram-negative bacterium [26].…”

CD90+ Stromal Cells are Non-Professional Innate Immune Effectors of the Human Colonic Mucosa

“…Interestingly, a similar synergy between NOD2 and TLR2 signaling is observed in cells from this site, whereby co-triggering with ligands of these PRRs synergistically enhances the expression of IL-6 and IL-8 via a p38MAPK-dependent mechanism (16). Synergy in multiple PRR signaling pathways has also been reported (17), and it has been suggested that such synergy may be specific to the TLR2 and NOD2 signaling pathways in stromal cells isolated from the oral mucosa (18, 19). A major outstanding question is whether the signaling pathways underlying the synergy between simultaneous NOD2 and TLR2 triggering are conserved between myeloid and stromal cells or whether cell type-specific pathways result in broadly similar transcriptional and functional outcomes.…”

NLRP3 inflammasome may regulate inflammatory response of human periodontal ligament fibroblasts in an apoptosis‐associated speck‐like protein containing a CARD (ASC)‐dependent manner

“…Previous studies reported TLR stimulation led to increased gene expression of NOD1 and NOD2 in HPDLFs (Jeon et al . ). Moreover, LPS pretreatment enhanced the activation of NF‐κB, ERK and JNK by MDP in hepatocytes (Scott et al .…”