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.

Abstract

To evaluate the anti-inflammatory effects of glutamine and the underlying signal pathway mechanisms in lipopolysaccharide (LPS)-stimulated human dental pulp cells (HDPCs). 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). 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. Glutamine exerted an anti-inflammatory effect via activation of MKP-1 and inhibition of the NF-κB and MAPK pathways in LPS-treated HDPCs.