Abstract
Curcumin, a yellow phytochemical found in the rhizomes of Curcuma longa, has various biological effects, including anti-oxidant and anti-inflammatory activities. In the present study, we examined the effect of curcumin on the expression of inflammatory cytokines in human gingival epithelial progenitor cells (HGEPs) stimulated for a prolonged period with lipopolysaccharide (LPS) derived from Porphyromonas gingivalis. The cells were alternately cultured with LPS and/or curcumin every 3 days for 18 days. The expression levels of TNF-α, IL-1β, IL-6, TIMP-1, and MMP-9 in the HGEPs were evaluated by quantitative real-time polymerase chain reaction. Enzyme-linked immunosorbent assay was used to measure the concentrations of these five proteins in the supernatant and nuclear factor (NF)-κB in the nuclear extracts. Curcumin inhibited the mRNA expression levels of TNF-α, IL-1β, IL-6, and MMP-9 in HGEPs treated with curcumin over a prolonged period. Similarly, the expression levels of IL-1β, IL-6, and MMP-9 were decreased in the culture supernatants. NF-κB activity was also inhibited in the cells cultured with curcumin. In conclusion, these findings indicate that curcumin inhibits the expression of inflammatory cytokines and MMP-9 in primary gingival epithelial cells stimulated with P. gingivalis-derived LPS via NF-κB activation.
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Huang TS, Lee SC, Lin JK. Suppression of c-Jun/AP-1 activation by an inhibitor of tumor promotion in mouse fibroblast cells. Proc Natl Acad Sci USA. 1991;88:5292–6.
Singh S, Aggarwal BB. Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane). J Biol Chem. 1995;270:24995–5000.
Abe Y, Hashimoto S, Horie T. Curcumin inhibition of inflammatory cytokine production by human peripheral blood monocytes and alveolar macrophages. Pharmacol Res. 1999;39:41–7.
Aggarwal BB, Shishodia S, Takada Y, Banerjee S, Newman RA, Bueso-Ramos CE, Price JE. Curcumin suppresses the paclitaxel-induced nuclear factor-kappaB pathway in breast cancer cells and inhibits lung metastasis of human breast cancer in nude mice. Clin Cancer Res. 2005;11:7490–8.
Bharti AC, Donato N, Aggarwal BB. Curcumin (diferuloylmethane) inhibits constitutive and IL-6-inducible STAT3 phosphorylation in human multiple myeloma cells. J Immunol. 2003;171:3863–71.
Shishodia S, Singh T, Chaturvedi MM. Modulation of transcription factors by curcumin. Adv Exp Med Biol. 2007;595:127–48.
Ryu MJ, Cho M, Song JY, Yun YS, Choi IW, Kim DE, Park BS, Oh S. Natural derivatives of curcumin attenuate the Wnt/beta-catenin pathway through down-regulation of the transcriptional coactivator p300. Biochem Biophys Res Commun. 2008;377:1304–8.
Nemmar A, Subramaniyan D, Ali BH. Protective effect of curcumin on pulmonary and cardiovascular effects induced by repeated exposure to diesel exhaust particles in mice. PLoS One. 2012;7:e39554.
Kanai M, Imaizumi A, Otsuka Y, Sasaki H, Hashiguchi M, Tsujiko K, Matsumoto S, Ishiguro H, Chiba T. Dose-escalation and pharmacokinetic study of nanoparticle curcumin, a potential anticancer agent with improved bioavailability, in healthy human volunteers. Cancer Chemother Pharmacol. 2012;69:65–70.
Guimarães MR, de Aquino SG, Coimbra LS, Spolidorio LC, Kirkwood KL, Rossa C Jr. Curcumin modulates the immune response associated with LPS-induced periodontal disease in rats. Innate Immun. 2012;18:155–63.
Gu Y, Lee HM, Napolitano N, Clemens M, Zhang Y, Sorsa T, Zhang Y, Johnson F, Golub LM. 4-methoxycarbonyl curcumin: a unique inhibitor of both inflammatory mediators and periodontal inflammation. Mediators Inflamm. 2013;2013:329740.
Elburki MS, Rossa C, Guimaraes MR, Goodenough M, Lee HM, Curylofo FA, Zhang Y, Johnson F, Golub LM. A novel chemically modified curcumin reduces severity of experimental periodontal disease in rats: initial observations. Mediators Inflamm. 2014;2014:959471.
Gottumukkala SN, Sudarshan S, Mantena SR. Comparative evaluation of the efficacy of two controlled release devices: chlorhexidine chips and indigenous curcumin based collagen as local drug delivery systems. Contemp Clin Dent. 2014;5:175–81.
Bhatia M, Urolagin SS, Pentyala KB, Urolagin SB, K B M, Bhoi S. Novel therapeutic approach for the treatment of periodontitis by curcumin. J Clin Diagn Res. 2014;8(12):ZC65–9. https://doi.org/10.7860/JCDR/2014/8231.5343.
Buduneli N, Kinane DF. Host-derived diagnostic markers related to soft tissue destruction and bone degradation in periodontitis. J Clin Periodontol. 2011;38:85–105.
Sorsa T, Mäntylä P, Tervahartiala T, Pussinen PJ, Gamonal J, Hernandez M. MMP activation in diagnostics of periodontitis and systemic inflammation. J Clin Periodontol. 2011;38:817–9.
Butler GS, Overall CM. Matrix metalloproteinase processing of signaling molecules to regulate inflammation. Periodontol. 2000;2013(63):123–48.
Heikkinen AM, Sorsa T, Pitkäniemi J, Tervahartiala T, Kari K, Broms U, Koskenvuo M, Meurman JH. Smoking affects diagnostic salivary periodontal disease biomarker levels in adolescents. J Periodontol. 2010;81:1299–307.
Ingman T, Sorsa T, Lindy O, Koski H, Konttinen YT. Multiple forms of gelatinases/type IV collagenases in saliva and gingival crevicular fluid of periodontitis patients. J Clin Periodontol. 1994;21:26–31.
Franco C, Patricia HR, Timo S, Claudia B, Marcela H. Matrix metalloproteinases as regulators of periodontal inflammation. Int J Mol Sci. 2017. https://doi.org/10.3390/ijms18020440.
Takai R, Uehara O, Harada F, Utsunomiya M, Chujo T, Yoshida K, Sato J, Nishimura M, Chiba I, Abiko Y. DNA hypermethylation of extracellular matrix-related genes in human periodontal fibroblasts induced by stimulation for a prolonged period with lipopolysaccharide derived from Porphyromonas gingivalis. J Periodontal Res. 2016;51:508–17.
Li S, Li C, Ryu HH, Lim SH, Jang WY, Jung S. Bacitracin inhibits the migration of U87-MG glioma cells via interferences of the integrin outside-in signaling pathway. J Korean Neurosurg Soc. 2016;59:106–16.
Jiang H, Deng Y, Wang T, Ma J, Li P, Tian P, Han C, Ma X. Interleukin-23 may contribute to the pathogenesis of lumbar disc herniation through the IL-23/IL-17 pathway. J Orthop Surg Res. 2016;11:12.
Chen KC, Wang YS, Hu CY, Chang WC, Liao YC, Dai CY, Juo SH. OxLDL up-regulates microRNA-29b, leading to epigenetic modifications of MMP-2/MMP-9 genes: a novel mechanism for cardiovascular diseases. FASEB J. 2011;25:1718–28.
Scrideli CA, Cortez MA, Yunes JA, Queiróz RG, Valera ET, da Mata JF, Toledo SR, Pavoni-Ferreira P, Lee ML, Petrilli AS, Brandalise SR, Tone LG. mRNA expression of matrix metalloproteinases (MMPs) 2 and 9 and tissue inhibitor of matrix metalloproteinases (TIMPs) 1 and 2 in childhood acute lymphoblastic leukemia: potential role of TIMP1 as an adverse prognostic factor. Leuk Res. 2010;34:32–7.
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25:402–8.
Moghadamtousi SZ, Kadir HA, Hassandarvish P, Tajik H, Abubakar S, Zandi K. A review on antibacterial, antiviral, and antifungal activity of curcumin. Biomed Res Int. 2014;2014:186864.
Tseng YH, Chang KW, Liu CJ, Lin CY, Yang SC, Lin SC. Areca nut extract represses migration and differentiation while activating matrix metalloproteinase-9 of normal gingival epithelial cells. J Periodontal Res. 2008;43:490–9.
Chen D, Nie M, Fan MW, Bian Z. Anti-inflammatory activity of curcumin in macrophages stimulated by lipopolysaccharides from Porphyromonas gingivalis. Pharmacology. 2008;82:264–9.
Smith PC, Santibañez JF, Morales JP, Martinez J. Epidermal growth factor stimulates urokinase-type plasminogen activator expression in human gingival fibroblasts. Possible modulation by genistein and curcumin. J Periodontal Res. 2004;39:380–7.
Jabłońska-Trypuć A, Matejczyk M, Rosochacki S. Matrix metalloproteinases (MMPs), the main extracellular matrix (ECM) enzymes in collagen degradation, as a target for anticancer drugs. J Enzyme Inhib Med Chem. 2016;31:177–83.
Lu LC, Yang CW, Hsieh WY, Chuang WH, Lin YC, Lin CS. Decreases in plasma MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios in uremic patients during hemodialysis. Clin Exp Nephrol. 2016;20:934–42.
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This study was supported in part by a Grant-in-Aid for the 2017–2018 Research Project of the Research Institute of Personalized Health Sciences, Health Sciences University of Hokkaido.
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Toraya, S., Uehara, O., Hiraki, D. et al. Curcumin inhibits the expression of proinflammatory mediators and MMP-9 in gingival epithelial cells stimulated for a prolonged period with lipopolysaccharides derived from Porphyromonas gingivalis. Odontology 108, 16–24 (2020). https://doi.org/10.1007/s10266-019-00432-8
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DOI: https://doi.org/10.1007/s10266-019-00432-8