Effects of IL-1β on MMP-9 Expression in Cementoblast-Derived Cell Line and MMP-Mediated Degradation of Type I Collagen
- 58 Downloads
It has been reported that matrix metalloproteinases (MMPs) are induced by many cytokines, and they are involved in various inflammatory processes, including periodontitis. However, the effects of interleukin-1β (IL-1β) on MMP-9 expression in cementoblasts, the cells responsible for cementum production, remain largely unknown. In this study, we used qPCR and gelatin zymogram analysis to show that IL-1β upregulated MMP-9 expression in cementoblast-derived cell line. Several signaling pathways, such as ERK1/2, JNK, p38, and AP-1 (c-Fos and ATF-2), were activated in response to IL-1β stimulation. Furthermore, enhancement of AP-1 activity by IL-1β was further confirmed by the AP-1 reporter assay and the electrophoretic mobility shift assay (EMSA). Pretreatment with specific inhibitors of ERK1/2 (U0126), JNK (SP600125), and AP-1 (tanshinone IIA) attenuated IL-1β-induced MMP-9 expression. In addition, inhibitors of ERK1/2 (U0126) and JNK (SP600125) attenuated IL-1β-enhanced AP-1 activity. This suggested that IL-1β stimulated AP-1 activation, at least partially, through ERK1/2 and JNK signaling pathways. Moreover, we found that IL-1β also upregulated the expression of MMP-13 and enhanced MMP-mediated degradation of type I collagen. Collectively, these results suggested that IL-1β induced MMP-9 expression by activation of AP-1 through the ERK1/2 and JNK signaling pathways in cementoblast-derived cell line and enhanced MMP-mediated collagen degradation possibly by MMP-13 and MMP-9.
KEY WORDSinterleukin-1β MAPK signaling pathway dental cementum matrix metalloproteinases cell-mediated collagen degradation
Mingyuan Du contributed to conception and design, contributed to data acquisition, analysis, and interpretation, and drafted the manuscript. Yunlong Wang, Zhingjian Liu, Leilei Wang, Zhengguo Cao contributed to conception and design; Chen Zhang and Hong He contributed to data analysis and interpretation; Yunlong Wang and Yunru Hao contributed to acquisition. All authors critically revised the manuscript, gave final approval, and agree to be accountable for all aspects of the work, ensuring integrity and accuracy.
This study was financially supported by grants from the National Natural Science Foundation of China (Nos. 81671020, 81200811, and 81701013).
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
- 8.Bernard, Y., C. Melchior, E. Tschirhart, and J.L. Bueb. 2008. Co-cultures of human coronary smooth muscle cells and dimethyl sulfoxide-differentiated HL60 cells upregulate ProMMP9 activity and promote mobility-modulation by reactive oxygen species. Inflammation 31 (5): 287–298. https://doi.org/10.1007/s10753-008-9077-z.CrossRefGoogle Scholar
- 11.Hernandez, M., M.A. Valenzuela, C. Lopez-Otin, J. Alvarez, J.M. Lopez, R. Vernal, and J. Gamonal. 2006. Matrix metalloproteinase-13 is highly expressed in destructive periodontal disease activity. Journal of Periodontology 77 (11): 1863–1870. https://doi.org/10.1902/jop.2006.050461.CrossRefGoogle Scholar
- 12.Hernandez, M., N. Dutzan, J. Garcia-Sesnich, L. Abusleme, A. Dezerega, N. Silva, F.E. Gonzalez, R. Vernal, T. Sorsa, and J. Gamonal. 2011. Host-pathogen interactions in progressive chronic periodontitis. Journal of Dental Research 90 (10): 1164–1170. https://doi.org/10.1177/0022034511401405.CrossRefGoogle Scholar
- 13.Sorsa, T., U.K. Gursoy, S. Nwhator, M. Hernandez, T. Tervahartiala, J. Leppilahti, M. Gursoy, E. Könönen, G. Emingil, P.J. Pussinen, and P. Mäntylä. 2016. Analysis of matrix metalloproteinases, especially MMP-8, in gingival creviclular fluid, mouthrinse and saliva for monitoring periodontal diseases. Periodontology 2000 70 (1): 142–163. https://doi.org/10.1111/prd.12101.CrossRefGoogle Scholar
- 16.Kubota, T., M. Itagaki, C. Hoshino, M. Nagata, T. Morozumi, T. Kobayashi, R. Takagi, and H. Yoshie. 2008. Altered gene expression levels of matrix metalloproteinases and their inhibitors in periodontitis-affected gingival tissue. Journal of Periodontology 79 (1): 166–173. https://doi.org/10.1902/jop.2008.070159.CrossRefGoogle Scholar
- 17.Kusano, K., C. Miyaura, M. Inada, T. Tamura, A. Ito, H. Nagase, K. Kamoi, and T. Suda. 1998. Regulation of matrix metalloproteinases (MMP-2, −3, −9, and −13) by interleukin-1 and interleukin-6 in mouse calvaria: association of MMP induction with bone resorption. Endocrinology 139 (3): 1338–1345. https://doi.org/10.1210/endo.139.3.5818.CrossRefGoogle Scholar
- 18.Shi, J., E. Schmitt-Talbot, D.A. DiMattia, and R.G. Dullea. 2004. The differential effects of IL-1 and TNF-alpha on proinflammatory cytokine and matrix metalloproteinase expression in human chondrosarcoma cells. Inflammation Research 53 (8): 377–389. https://doi.org/10.1007/s00011-004-1271-3.CrossRefGoogle Scholar
- 19.Fujisaki, K., N. Tanabe, N. Suzuki, T. Kawato, O. Takeichi, O. Tsuzukibashi, M. Makimura, K. Ito, and M. Maeno. 2007. Receptor activator of NF-kappaB ligand induces the expression of carbonic anhydrase II, cathepsin K, and matrix metalloproteinase-9 in osteoclast precursor RAW264.7 cells. Life Sciences 80 (14): 1311–1318. https://doi.org/10.1016/j.lfs.2006.12.037.CrossRefGoogle Scholar
- 20.Suh, S.J., C.H. Kwak, K.H. Song, K.M. Kwon, T.W. Chung, S.H. Cho, Y.K. Kim, et al. 2012. Triple inhibitory activity of Cliona celata against TNF-alpha-induced matrix metalloproteinase-9 production via downregulated NF-kappaB and AP-1, enzyme activity, and migration potential. Inflammation 35 (2): 736–745. https://doi.org/10.1007/s10753-011-9369-6.CrossRefGoogle Scholar
- 22.Sanchavanakit, N., W. Saengtong, J. Manokawinchoke, and P. Pavasant. 2015. TNF-alpha stimulates MMP-3 production via PGE2 signalling through the NF-kB and p38 MAPK pathway in a murine cementoblast cell line. Archives of Oral Biology 60 (7): 1066–1074. https://doi.org/10.1016/j.archoralbio.2015.04.001.CrossRefGoogle Scholar
- 23.Wang, Y.L., H. He, Z.J. Liu, Z.G. Cao, X.Y. Wang, K. Yang, Y. Fang, M. Han, C. Zhang, and F.Y. Huo. 2015. Effects of TNF-alpha on Cementoblast differentiation, mineralization, and apoptosis. Journal of Dental Research 94 (9): 1225–1232. https://doi.org/10.1177/0022034515590349.CrossRefGoogle Scholar
- 27.Lin, H.Y., B.R. Wells, R.E. Taylor, and H. Birkedal-Hansen. 1987. Degradation of type I collagen by rat mucosal keratinocytes. Evidence for secretion of a specific epithelial collagenase. The Journal of Biological Chemistry 262 (14): 6823–6831.Google Scholar
- 29.Martin, G., P. Bogdanowicz, F. Domagala, H. Ficheux, and J.P. Pujol. 2003. Rhein inhibits interleukin-1 beta-induced activation of MEK/ERK pathway and DNA binding of NF-kappa B and AP-1 in chondrocytes cultured in hypoxia: a potential mechanism for its disease-modifying effect in osteoarthritis. Inflammation 27 (4): 233–246.CrossRefGoogle Scholar
- 30.Van den Steen, P.E., B. Dubois, I. Nelissen, P.M. Rudd, R.A. Dwek, and G. Opdenakker. 2002. Biochemistry and molecular biology of gelatinase B or matrix metalloproteinase-9 (MMP-9). Critical Reviews in Biochemistry and Molecular Biology 37 (6): 375–536. https://doi.org/10.1080/10409230290771546.CrossRefGoogle Scholar
- 31.Liang, K.C., C.W. Lee, W.N. Lin, C.C. Lin, C.B. Wu, S.F. Luo, and C.M. Yang. 2007. Interleukin-1beta induces MMP-9 expression via p42/p44 MAPK, p38 MAPK, JNK, and nuclear factor-kappaB signaling pathways in human tracheal smooth muscle cells. Journal of Cellular Physiology 211 (3): 759–770. https://doi.org/10.1002/jcp.20992.CrossRefGoogle Scholar
- 33.Lin, C.C., C.T. Kuo, C.Y. Cheng, C.Y. Wu, C.W. Lee, H.L. Hsieh, I.T. Lee, and C.M. Yang. 2009. IL-1 beta promotes A549 cell migration via MAPKs/AP-1- and NF-kappaB-dependent matrix metalloproteinase-9 expression. Cellular Signalling 21 (11): 1652–1662. https://doi.org/10.1016/j.cellsig.2009.07.002.CrossRefGoogle Scholar
- 35.Aimes, R.T., and J.P. Quigley. 1995. Matrix metalloproteinase-2 is an interstitial collagenase. Inhibitor-free enzyme catalyzes the cleavage of collagen fibrils and soluble native type I collagen generating the specific 3/4- and 1/4-length fragments. The Journal of Biological Chemistry 270 (11): 5872–5876.CrossRefGoogle Scholar
- 38.Huhtala, P., L.T. Chow, and K. Tryggvason. 1990. Structure of the human type IV collagenase gene. The Journal of Biological Chemistry 265 (19): 11077–11082.Google Scholar
- 39.Huhtala, P., L. Chow, T. Shows, and K. Tryggvason. 1992. Structure of the human 70 K type IV collagenase gene and assignment of the gene to the q21 region of chromosome 16. Matrix Supplement 1: 84.Google Scholar
- 40.Tseng, H.C., I.T. Lee, C.C. Lin, P.L. Chi, S.E. Cheng, R.H. Shih, L.D. Hsiao, and C.M. Yang. 2013. IL-1beta promotes corneal epithelial cell migration by increasing MMP-9 expression through NF-kappaB- and AP-1-dependent pathways. PLoS One 8 (3): e57955. https://doi.org/10.1371/journal.pone.0057955.CrossRefGoogle Scholar
- 42.Wu, C.Y., H.L. Hsieh, M.J. Jou, and C.M. Yang. 2004. Involvement of p42/p44 MAPK, p38 MAPK, JNK and nuclear factor-kappa B in interleukin-1beta-induced matrix metalloproteinase-9 expression in rat brain astrocytes. Journal of Neurochemistry 90 (6): 1477–1488. https://doi.org/10.1111/j.1471-4159.2004.02682.x.CrossRefGoogle Scholar
- 43.Huang, Q., F. Lan, X. Wang, Y. Yu, X. Ouyang, F. Zheng, J. Han, Y. Lin, Y. Xie, F. Xie, W. Liu, X. Yang, H. Wang, L. Dong, L. Wang, and J. Tan. 2014. IL-1beta-induced activation of p38 promotes metastasis in gastric adenocarcinoma via upregulation of AP-1/c-fos, MMP2 and MMP9. Molecular Cancer 13: 18. https://doi.org/10.1186/1476-4598-13-18.CrossRefGoogle Scholar
- 48.Zijlstra, A., R.T. Aimes, D. Zhu, K. Regazzoni, T. Kupriyanova, M. Seandel, E.I. Deryugina, and J.P. Quigley. 2004. Collagenolysis-dependent angiogenesis mediated by matrix metalloproteinase-13 (collagenase-3). The Journal of Biological Chemistry 279 (26): 27633–27645. https://doi.org/10.1074/jbc.M313617200.CrossRefGoogle Scholar