Brain-Derived Neurotrophic Factor Inhibits Peptidoglycan-Induced Inflammatory Cytokine Expression in Human Dental Pulp Cells
- 218 Downloads
The aim of this study was to examine the anti-inflammatory effect of brain-derived neurotrophic factor (BDNF) on human dental pulp cells (HDPCs) and identify the intracellular signaling pathway involved. We investigated the effect of BDNF (50 ng/ml) on interleukin (IL)-6 and IL-8 expression in peptidoglycan (PGN)-treated HDPCs. An inhibition assay was performed with MAPK or NF-κB inhibitors to determine the possible signaling pathway. IL-6 and IL-8 mRNA, IL-6 and IL-8 protein, and phosphorylated p38 kinase activity were determined using real-time PCR, ELISA, and Western blot analysis, respectively. BDNF significantly attenuated PGN-induced IL-6 and IL-8 mRNA and protein levels in HDPCs. A p38 inhibitor also inhibited IL-6 and IL-8 mRNA transcription. PGN stimulated phosphorylated p38 kinase activity in HDPCs, which was inhibited by BDNF. Suppression of phosphorylated p38 kinase activity by BDNF in HDPCs inhibited increased IL-6 and IL-8 expression induced by PGN. Our findings suggest that BDNF regulates intracellular signaling molecule activities to exert its anti-inflammatory effect.
KEY WORDSbrain-derived neurotrophic factor peptidoglycan pulp cells endodontic treatment
This work was supported in part by JSPS KAKENHI Grant Number JP25463218.
- 2.Ghoddusi, J., M. Forghani, and I. Parisay. 2014. New approaches in vital pulp therapy in permanent teeth. Iranian Endodontic J 9: 15–22.Google Scholar
- 4.Ko, Y.J., K.Y. Kwon, K.Y. Kum, W.C. Lee, S.H. Baek, M.K. Kang, et al. 2015. The anti-inflammatory effect of human telomerase-derived peptide on P. gingivalis lipopolysaccharide-induced inflammatory cytokine production and its mechanism in human dental pulp cells. Mediators Inflammation 2015: 385127.Google Scholar
- 16.Kerschensteiner, M., E. Gallmeier, L. Behrens, V.V. Leal, T. Misgeld, W.E. Klinkert, et al. 1999. Activated human T cells, B cells, and monocytes produce brain-derived neurotrophic factor in vitro and in inflammatory brain lesions: a neuroprotective role of inflammation? Journal of Experimental Medicine 189: 865–70.CrossRefPubMedPubMedCentralGoogle Scholar
- 22.Juarez-Verdayes, M.A., S. Rodriguez-Martinez, M.E. Cancino-Diaz, and J.C. Cancino-Diaz. 2013. Peptidoglycan and muramyl dipeptide from Staphylococcus aureus induce the expression of VEGF-A in human limbal fibroblasts with the participation of TLR2-NFkappaB and NOD2-EGFR. Graefes Archive for Clinical and Experimental Ophthalmology 251: 53–62.CrossRefGoogle Scholar
- 23.Ji, X.C., Y.Y. Dang, H.Y. Gao, Z.T. Wang, M. Gao, Y. Yang, et al. 2015. Local Injection of Lenti-BDNF at the Lesion Site Promotes M2 Macrophage Polarization and Inhibits Inflammatory Response After Spinal Cord Injury in Mice. Cellular and Molecular Neurobiology 35: 881–90.CrossRefPubMedGoogle Scholar
- 28.Chen, B.C., C.C. Liao, M.J. Hsu, Y.T. Liao, C.C. Lin, J.R. Sheu, et al. 2006. Peptidoglycan-induced IL-6 production in RAW 264.7 macrophages is mediated by cyclooxygenase-2, PGE2/PGE4 receptors, protein kinase A, I kappa B kinase, and NF-kappa B. Journal of Immunology 177: 681–93.CrossRefGoogle Scholar