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The Anti‐Inflammatory Role of Heme Oxygenase‐1 in Lipopolysaccharide and Cytokine‐Stimulated Inducible Nitric Oxide Synthase and Nitric Oxide Production in Human Periodontal Ligament Cells
Author(s) -
Kim YoungSuk,
Pi SungHee,
Lee YoungMan,
Lee SangIm,
Kim EunCheol
Publication year - 2009
Publication title -
journal of periodontology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.036
H-Index - 156
eISSN - 1943-3670
pISSN - 0022-3492
DOI - 10.1902/jop.2009.090145
Subject(s) - nitric oxide , heme oxygenase , nitric oxide synthase , lipopolysaccharide , chemistry , heme , periodontal fiber , cytokine , microbiology and biotechnology , biochemistry , enzyme , medicine , immunology , biology , dentistry , organic chemistry
Background: Although heme oxygenase‐1 (HO‐1) is involved in anti‐inflammation, the mechanisms of its activity in regulating periodontal inflammation are largely unclear. Therefore, the aim of this study is to investigate the anti‐inflammatory properties of HO‐1 in lipopolysaccharide (LPS)‐ and proinflammatory cytokine‐stimulated inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production in human periodontal ligament (PDL) cells. Methods: PDL cells were treated with LPS plus a combination of tumor necrosis factor (TNF)‐α and interleukin (IL)‐1β in serum‐free media for 1 day. The production of NO was evaluated using a Griess reagent kit. The expression of iNOS and HO‐1 proteins and mRNAs was evaluated using Western blotting and reverse transcriptase‐polymerase chain reaction, respectively. Results: Proinflammatory cytokines and LPS triggered iNOS and HO‐1 expression and NO production in PDL cells. HO‐1 inhibitor and HO‐1 small interfering RNA (siRNA) attenuated the LPS‐ and cytokine‐stimulated NO release and iNOS and HO‐1 expression. Specific inhibitors of p38, extracellular signal‐regulated kinase (ERK), and c‐Jun N‐terminal kinase (JNK) mitogen‐activated protein kinases phosphatidylinositol 3‐kinase (PI3K), nuclear factor‐kappa B (NF‐κB), and protein kinase C delta (PKC‐δ) greatly reduced the levels of iNOS and HO‐1 expression induced by LPS plus cytokines. Conclusions: Collectively, these data suggested that HO‐1 inhibition blocked LPS‐ and proinflammatory cytokine‐stimulated iNOS expression and NO production in PDL cells via a mechanism that involves p38, ERK, PI3K, NF‐κB, and PKC‐δ. Thus, the regulation of HO‐1 activity may be a therapeutic strategy for periodontal disease.