Anti-inflammatory effects of glutamine on LPS-stimulated human dental pulp cells correlate with activation of MKP-1 and attenuation of the MAPK and NF-κB pathways.
OBJECTIVE
To evaluate the anti-inflammatory effects of glutamine and the underlying signal pathway mechanisms in lipopolysaccharide (LPS)-stimulated human dental pulp cells (HDPCs).


METHODS
Human dental pulp cells were exposed to 10 μg mL(-1) LPS and various concentrations of glutamine for 24 h. The production of PGE2 and nitric oxide was determined by enzyme-linked immunosorbent assay (ELISA) and Griess reagent kit, respectively. Cytokines were examined by ELISA, reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time PCR. iNOS and COX protein expression as well as signal pathways were accessed by Western blot. The data were analysed by anova with Bonferroni's test (α = 0.05).


RESULTS
Glutamine reduced LPS-induced iNOS and COX-2 protein expression as well as production of NO and PGE2 in a dose-dependent fashion. Additionally, glutamine suppressed the production and mRNA expression of inflammatory cytokines including interleukin-1β (IL-1β), TNF-α, and IL-8. Furthermore, glutamine attenuated phosphorylation of extracellular signal-regulated kinase (ERK), p38, c-Jun N-terminal kinase (JNK) and IκB-α, and nuclear translocation of NF-κB p65, but enhanced mitogen-activated protein kinase phosphatase-1 (MKP-1) expression in LPS-treated HDPCs.


CONCLUSIONS
Glutamine exerted an anti-inflammatory effect via activation of MKP-1 and inhibition of the NF-κB and MAPK pathways in LPS-treated HDPCs.
Department of Conservative Dentistry, School of Dentistry, Kyung Hee University, Seoul, Korea.
D-S
DS
Kim
M-R
MR
Shin
Y-S
YS
Kim
W-J
WJ
Bae
D-H
DH
Roh
Y-S
YS
Hwang
E-C
EC
Kim
D015153:Blotting, Western; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003782:Dental Pulp / Q000166:cytology* / Q000378:metabolism*; D054638:Dual Specificity Phosphatase 1 / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005973:Glutamine / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control*; D008070:Lipopolysaccharides / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D005973:Glutamine; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1
MKP-1; NF-κB; glutamine; human dental pulp cells; lipopolysaccharide; mitogen-activated protein kinase; pro-inflammatory mediators