NOD1 and NOD2 stimulation triggers innate immune responses of human             periodontal ligament cells.
Nod-like receptors (NLRs) are cytosolic sensors for microbial molecules.             Νucleotide-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.
Department of Pathology and Research Center for Oral Disease                     Regulation of the Aged, School of Dentistry, Chosun University, Gwangju                     501-759, Republic of Korea.
Do-In
DI
Jeon
Se-Ra
SR
Park
Mee-Young
MY
Ahn
Sang-Gun
SG
Ahn
Jong-Hwan
JH
Park
Jung-Hoon
JH
Yoon
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D003960:Diaminopimelic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D053474:Nod1 Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism*; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism*; D009842:Oligopeptides / Q000235:genetics / Q000378:metabolism; D010513:Periodontal Ligament / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism
D015850:Interleukin-6; D016209:Interleukin-8; C555437:L-Ala-gamma-D-Glu-meso-diaminopimelic acid; D016328:NF-kappa B; C119067:NOD1 protein, human; C429018:NOD2 protein, human; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D009842:Oligopeptides; D051193:Toll-Like Receptors; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D003960:Diaminopimelic Acid; D007371:Interferon-gamma