Nicotine and lipopolysaccharide stimulate the production of MMPs and prostaglandin E2 by hypoxia-inducible factor-1α up-regulation in human periodontal ligament cells

Journal of Periodontal Research
Y-S KimE-C Kim

Abstract

Although hypoxia-inducible factor 1α (HIF-1α) is up-regulated in the periodontal pockets of periodontitis patients, the expression and precise molecular mechanisms of HIF-1α remain unknown in human periodontal ligament cells (PDLCs). The aim of this study was to explore the effects, as well as the signaling pathway, of nicotine and lipopolysaccharide (LPS) on the expression of HIF-1α and on the production of its target genes, including cyclooxygenase-2 (COX-2)-derived prostaglandin E(2) (PGE(2) ), MMP-2 and MMP-9 in PDLCs. The expression of COX-2 and HIF-1α proteins was evaluated using western blotting. The production of PGE(2) and MMPs was evaluated using enzyme immunoassays and zymography, respectively. LPS and nicotine synergistically induced the production of PGE(2) , MMP-2 and MMP-9, and increased the expression of MMP-2, MMP-9, COX-2 and HIF-1α proteins. Inhibition of HIF-1α activity by chetomin or knockdown of HIF1α gene expression by small interfering RNA markedly attenuated the production of LPS- and nicotine-stimulated PGE(2) and MMPs, as well as the expression of COX-2 and HIF-1α. Furthermore, pretreatment with inhibitors of COX-2, p38, extracellular signal-regulated kinase, Jun N-terminal kinase, protein kinase C, p...Continue Reading

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Citations

Apr 23, 2013·Gene Expression Patterns : GEP·Cheol-Hyeon BaeEui-Sic Cho
Apr 9, 2013·The Journal of Allergy and Clinical Immunology·Dihan ZhuKe Zen
Oct 23, 2016·Dental Materials : Official Publication of the Academy of Dental Materials·Eun-Cheol KimSu-Jin Ahn
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Jun 9, 2019·Acta Odontologica Scandinavica·Mehmet Murat TaskanFatma Ucan Yarkac
Feb 18, 2020·Frontiers in Microbiology·Yaling JiangMingyun Li
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Jan 14, 2021·International Journal of Environmental Research and Public Health·Na AnXiaohui Rausch-Fan
Mar 5, 2021·Journal of Periodontology·Chiaki MorimotoShinya Murakami

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