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Kim Y-S, Shin S-I, Kang K-L, Herr Y, Bae W-J, Kim E-C. Nicotine and lipopolysaccharide stimulate the production of MMPs and prostaglandin E2 by hypoxia-inducible factor-1α up-regulation in human periodontal ligament cells. J Periodont Res 2012; 47: 719-728. © 2012 John Wiley & Sons A/S Background and Objective: 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 E2 (PGE2), MMP-2 and MMP-9 in PDLCs. Material and Methods: The expression of COX-2 and HIF-1α proteins was evaluated using western blotting. The production of PGE2 and MMPs was evaluated using enzyme immunoassays and zymography, respectively. Results: LPS and nicotine synergistically induced the production of PGE2, 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 PGE2 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, phosphatidylinositol 3-kinase and nuclear factor-kappaB decreased the expression of nicotine- and LPS-induced HIF-1α and COX-2, as well as the activity of PGE2 and MMPs. Conclusion: These data demonstrate novel mechanisms by which nicotine and LPS promote periodontal tissue destruction, and provide further evidence that HIF-1α is a potential target in periodontal disease associated with smoking and dental plaque. [ABSTRACT FROM AUTHOR]

Background Recent investigations suggest that prostaglandin E2 (PGE2) is important in the pathogenesis of not only aspirin-intolerant asthma but also asthma unrelated to aspirin intolerance. Objectives This study was conducted to evaluate the effects of variations in the gene coding PGE2 receptor subtype EP1–4 ( Ptger1–4) on the risk of asthma in the Korean population. Methods Nineteen single nucleotide polymorphisms (SNPs) were selected after re-sequencing Ptger1–4 and were genotyped in 480 asthmatics and 140 healthy controls, who were randomly recruited. Results By logistic regression analyses controlling for age and sex, 1388T>C in Ptger3 was found to be significantly associated with asthma [ P=0.002, odds ratio (95% confidence interval)=0.63 (0.46–0.85) in the allele model], and this remained significant after applying the Bonferroni correction. In terms of haplotype, the frequency of the C–C–A–A haplotype in Ptger3 was significantly lower in asthmatics than in healthy controls ( P=0.004). Moreover, the prevalence of this haplotype was significantly lower in moderate-to-severe asthmatics than in mild asthmatics ( P=0.045; mild vs. moderate and P=0.034; mild vs. severe). However, no association was found between any genetic variation in Ptger1, Ptger2, or Ptger4 and asthma. Conclusion The present study demonstrated that genetic variations in Ptger3 are significantly associated with the risk and severity of asthma in the Korean population. [ABSTRACT FROM AUTHOR]