ABSTRACT
Periodontal disease is a common infectious disease that can lead to the loss of teeth. Hower how to effectively suppress the inflammation with medication is unclear. The aim of the present study was to investigate the antiinï¬ammatory effect of Oroxylin A in periodontitis and its potential role through heme oxygenase1 (HO1). Primary rat gingival fibroblasts (RGFs) were cultured using the tissue block method and identified by immunofluorescence. Following lipopolysaccharide (LPS) stimulation of RGFs, Oroxylin A was administered at 50, 100, 200 or 400 µg/ml. Reverse transcriptionquantitative PCR was used to assess mRNA expression of cyclooxygenase (COX)2, TNFα, RANKL and osteoprotegerin (OPG). Western blotting was used to detect protein expression levels of COX 2, TNFα, RANKL and OPG. Following HO1 knockdown, the same treatment was performed. The expression of COX2 in rat gingival tissue was observed by immunohistochemistry. Oneway analysis of variance and Student's t test were used for statistical analysis. Oroxylin A downregulated mRNA expression of COX2, TNFα, RANKL and OPG in LPSinduced RGFs. With increase of Oroxylin A dose, the expression of HO1 was gradually upregulated. When HO1 was knocked down, Oroxylin A did not downregulate the expression of COX2, TNFα, RANKL and OPG in LPSinduced RGFs. Immunohistochemical results showed that expression of COX2 was downregulated by Oroxylin A, and the expression of TNFα, RANKL and OPG were also downregulated. Oroxylin A decreased expression of inflammatory cytokines in LPSinduced RGFs and had a good inhibitory effect on periodontitis in rats.
Subject(s)
Cyclooxygenase 2 , Fibroblasts , Flavonoids , Periodontitis , RANK Ligand , Animals , Rats , Flavonoids/pharmacology , Periodontitis/metabolism , Periodontitis/drug therapy , Periodontitis/pathology , RANK Ligand/metabolism , RANK Ligand/genetics , Male , Cyclooxygenase 2/metabolism , Cyclooxygenase 2/genetics , Fibroblasts/metabolism , Fibroblasts/drug effects , Osteoprotegerin/metabolism , Osteoprotegerin/genetics , Lipopolysaccharides , Gingiva/metabolism , Gingiva/drug effects , Tumor Necrosis Factor-alpha/metabolism , Cytokines/metabolism , Heme Oxygenase-1/metabolism , Heme Oxygenase-1/genetics , Cells, Cultured , Rats, Sprague-DawleyABSTRACT
INTRODUCTION: Matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) are considered important mediators of the periapical immune response to infection. This study aimed to clarify the putative relationship between MMPs and TIMPs by elucidating the activity of MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1, and TIMP-2 in the temporal development of apical periodontitis (AP) in mice. METHODS: AP was induced in the lower first molars of 30 male Kunming mice. The animals were randomly killed at 0, 7, 14, 28, 60, and 90 days after pulp exposure. The jaws were removed and subjected to quantitative real-time reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemical analysis. RESULTS: The MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1, and TIMP-2 messenger RNA and protein expression levels increased with periapical inflammation progression (P < .05). The MMP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2 messenger RNA and protein expression levels increased during the acute and chronic stages of periapical lesions, with less MMP-2 and MMP-9 expression levels at the chronic stage (P < .05). The MMP-8 expression increased at the chronic stage of inflammation (P < .05) but not at the acute stage. Immunostained MMP-2 and TIMP-1 were observed in all experimental periods. CONCLUSIONS: MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1, and TIMP-2 were expressed in all periapical samples with varying levels between them. MMP expression could be related to TIMP expression in the temporal development of AP.
Subject(s)
Periapical Periodontitis , Tissue Inhibitor of Metalloproteinase-1 , Animals , Inflammation , Male , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 9 , Matrix Metalloproteinases/genetics , Mice , Tissue Inhibitor of Metalloproteinase-1/geneticsABSTRACT
Sjogren's syndrome (SS) is a systemic, autoimmune disorder characterized by salivary insufficiency and lymphocytic infiltration of the exocrine glands. Even though the mechanism of its pathology and progression has been researched ever since its discovery, the roles of different parts of immune system remain inconclusive. There is no straightforward and simple theory for the pathogenesis and diagnosis of Sjogren's syndrome because of the multiple kinds and functions of autoantibodies, changing proportion of different T-lymphocyte subsets with the progression of disease, unsuspected abilities of B lymphocytes discovered recently, crosstalk between cytokines connecting the factors mentioned previously, and genetic predisposition that contributes to the initiation of this disease. On the other hand, the number of significant reports and open-label studies of B-cell depletion therapy showing clinical efficacy in sjogren's syndrome has continued to accumulate, which provides a promising future for the patients. In a word, further elucidation of the role of different components of the immune system will open avenues for better diagnosis and treatment of SS, whose current management is still mainly supportive.
