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Effects of sirtuin 1 activation on nicotine and lipopolysaccharide‐induced cytotoxicity and inflammatory cytokine production in human gingival fibroblasts
Author(s) -
Park GJ.,
Kim YS.,
Kang Kl.,
Bae SJ.,
Baek HS.,
Auh QS.,
Chun YH.,
Park BH.,
Kim EC.
Publication year - 2013
Publication title -
journal of periodontal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.31
H-Index - 83
eISSN - 1600-0765
pISSN - 0022-3484
DOI - 10.1111/jre.12030
Subject(s) - proinflammatory cytokine , resveratrol , sirtuin 1 , mapk/erk pathway , chemistry , p38 mitogen activated protein kinases , lipopolysaccharide , protein kinase a , cytokine , cytotoxicity , pharmacology , kinase , microbiology and biotechnology , inflammation , biology , endocrinology , biochemistry , immunology , downregulation and upregulation , in vitro , gene
Background and Objective Although sirtuin 1 ( SIRT 1) over‐expression and resveratrol exert anti‐inflammatory and proinflammatory effects, their effects and the mechanism of action on human gingival fibroblast ( HGF )‐mediated inflammation are unknown. The aim of this study was to demonstrate the effects of activating SIRT 1 using resveratrol and recombinant adenovirus encoding SIRT 1 (Ad‐ SIRT 1) on the expression of proinflammatory cytokines and to elucidate its mechanism of action of lipopolysaccharide ( LPS ) and nicotine stimulated‐ HGF . Material and Methods Cytotoxicity and the production of reactive oxygen species (ROS) were measured using the 3‐(4,5‐dimethylthiazolyl‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay and flow cytometry, respectively. The amount of prostaglandin E 2 (PGE 2 ) released into the culture medium was measured by radioimmunoassay. mRNA and protein levels were analyzed using RT‐PCR and western blotting, respectively. Results Nicotine and LPS up‐regulated the expression of SIRT1 mRNA and SIRT1 protein in a time‐ and concentration‐dependent manner. Resveratrol and Ad‐SIRT1 decreased LPS and nicotine‐induced cytotoxicity, ROS and PGE 2 production, and expression of cyclooxygenase‐2 in HGFs. Resveratrol and Ad‐SIRT1 inhibited nicotine and LPS‐mediated protein kinase C (PKC), phosphatidylinositol 3‐kinase (PI3K), p38, ERK, JNK, MAPK and nuclear factor‐kappa B (NF‐κB) activation. Conclusion This study is the first to show that the anti‐inflammatory and cytoprotective effects of SIRT 1 activation in HGFs occur through the PKC , PI 3K, MAPK and NF ‐κB pathways.