JAK/STAT Pathway Modulates on Porphyromonas gingivalis Lipopolysaccharide- and Nicotine-Induced Inflammation in Osteoblasts
1
조회
0
다운로드
2
인용
0
참고문헌
키워드
초록
Bacterial infection and smoking are an important risk factors involved in the development and progression of periodontitis. However, the signalingmechanism underlying the host immune response is not fully understood in periodontal lesions. In this study, we determined the expression of januskinase (JAK)/signal transducer and activator of transcription (STAT) on Porphyromonas gingivalis lipopolysaccharide (LPS)- and nicotine-inducedcytotoxicity and the production of inflammatory mediators, using osteoblasts. The cells were cultured with 5 mM nicotine in the presence of 1 μg/mlLPS. Cell viability was determined using MTT assay. The role of JAK on inflammatory mediator expression and production, and the regulatorymechanisms involved were assessed via enzyme-linked immunosorbent assay, reverse transcription-polymerase chain reaction, and Western blotanalysis. LPS- and nicotine synergistically induced the production of cyclooxgenase-2 (COX-2) and prostaglandin E2 (PGE2) and increased theprotein expression of JAK/STAT. Treatment with an JAK inhibitor blocked the production of COX-2 and PGE2 as well as the expression ofpro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin-1β (IL-1β), and IL-6 in LPS- and nicotine-stimulated osteoblasts. Theseresults suggest that JAK/STAT is closely related to the LPS- and nicotine-induced inflammatory effects and is likely to regulate the immune responsein periodontal disease associated with dental plaque and smoking.
Abstract
Bacterial infection and smoking are an important risk factors involved in the development and progression of periodontitis. However, the signalingmechanism underlying the host immune response is not fully understood in periodontal lesions. In this study, we determined the expression of januskinase (JAK)/signal transducer and activator of transcription (STAT) on Porphyromonas gingivalis lipopolysaccharide (LPS)- and nicotine-inducedcytotoxicity and the production of inflammatory mediators, using osteoblasts. The cells were cultured with 5 mM nicotine in the presence of 1 μg/mlLPS. Cell viability was determined using MTT assay. The role of JAK on inflammatory mediator expression and production, and the regulatorymechanisms involved were assessed via enzyme-linked immunosorbent assay, reverse transcription-polymerase chain reaction, and Western blotanalysis. LPS- and nicotine synergistically induced the production of cyclooxgenase-2 (COX-2) and prostaglandin E2 (PGE2) and increased theprotein expression of JAK/STAT. Treatment with an JAK inhibitor blocked the production of COX-2 and PGE2 as well as the expression ofpro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin-1β (IL-1β), and IL-6 in LPS- and nicotine-stimulated osteoblasts. Theseresults suggest that JAK/STAT is closely related to the LPS- and nicotine-induced inflammatory effects and is likely to regulate the immune responsein periodontal disease associated with dental plaque and smoking.
참고문헌 (26)
- Page RC, "The role of inflammatory mediators in the pathogenesis of periodontal disease", J Periodont Res, 26, pp.230~242 (1991)
- Zambon JJ, "Actinobacillus actinomycetemcomitans in human periodontal disease. Prevalence in patient groups and distribution of biotypes and serotypes within families", J Periodontol, 54, pp.707~711 (1983)
- 황수정, "흡연이 치은열구액 내 Matrix Metalloproteinase-9에 미치는 영향", 치위생과학회지, 11(4), pp.339~344 (2011), 한국치위생과학회
- Darveau RP, "The oral microbial consortium's interaction with the periodontal innate defense system", DNA Cell Biol, 28, pp.389~395 (2009)
- Ji S, "Bacterial invasion and persistence:critical events in the pathogenesis of periodontitis?", J Periodontal Res, 50, pp.570~585 (2015)
- Madianos PN, "Generation of inflammatory stimuli: how bacteria set up inflammatory responses in the gingiva", J Clin Periodontol, 32(Suppl 6), pp.57~71 (2005)
- Ohlrich EJ, "The immunopathogenesis of periodontal disease", Aust Dent J, 54(Suppl 1), pp.S2~S10 (2009)
- Prabhu A, "Detection of local and systemic cytokines in adult periodontitis", J Periodontol, 67, pp.515~522 (1996)
- Shoji M, "Lipopolysaccharide enhances the production of nicotine-induced prostaglandin E2 by an increase in cyclooxygenase-2 expression in osteoblasts", Acta Biochim Biophys Sin (Shanghai), 39, pp.163~172 (2007)
- Bergström J, "Tobacco smoking and chronic destructive periodontal disease", Odontology, 92, pp.1~8 (2004)
- Apatzidou DA, "Impact of smoking on the clinical, microbiological and immunological parameters of adult patients with periodontitis", J Clin Periodontol, 32, pp.973~983 (2005)
- Alpar B, "Nicotine-induced alterations in human primary periodontal ligament and gingiva fibroblast cultures", Clin Oral Investig, 2, pp.40~46 (1998)
- Kamer AR, "Nicotine induced proliferation and cytokine release in osteoblastic cells", Int J Mol Med, 17, pp.121~127 (2006)
- Makino A, "Nicotine involved in periodontal disease through influence on cytokine levels", FEMS Immunol Med Microbiol, 52, pp.282~286 (2008)
- Liu YC, "Cytokine responses against periodontal infection: protective and destructive roles", Periodontol 2000, 52, pp.163~206 (2010)
- Graves DT, "The contribution of interleukin-1 and tumor necrosis factor to periodontal tissue destruction", J Periodontol, 74, pp.391~401 (2003)
- Berglundh T, "Aspects of adaptive host response in periodontitis", J Clin Periodontol, 32(Suppl 6), pp.87~107 (2005)
- Roberts FA, "Profile of cytokine mRNA expression in chronic adult periodontitis", J Dent Res, 76, pp.1833~1839 (1997)
- Chaves de Souza JA, "SOCS3 expression correlates with severity of inflammation, expression of proinflammatory cytokines, and activation of STAT3 and p38 MAPK in LPS-induced inflammation in vivo", Mediators Inflamm, 2013, pp.650812~ (2013)
- Garcia de Aquino S, "Signaling pathways associated with the expression of inflammatory mediators activated during the course of two models of experimental periodontitis", Life Sci, 84, pp.745~754 (2009)
- Noguchi K, "The roles of cyclooxygenase-2 and prostaglandin E2 in periodontal disease", Periodontol 2000, 43, pp.85~101 (2007)
- 이상임, "NFATc Mediates Lipopolysaccharide and Nicotine-Induced Expression of iNOS and COX-2 in Human Periodontal Ligament Cells", 치위생과학회지, 15(6), pp.753~760 (2015), 한국치위생과학회
- Lee SK, "Sodium hydrogen sulfide inhibits nicotine and lipopolysaccharide-induced osteoclastic differentiation and reversed osteoblastic differentiation in human periodontal ligament cells", J Cell Biochem, 114, pp.1183~1193 (2013)
- 이상임, "The Role of NFATc1 on Osteoblastic Differentiation in Human Periodontal Ligament Cells", 치위생과학회지, 15(4), pp.488~494 (2015), 한국치위생과학회
- Starr R, "Negative regulation of the JAK", STAT pathway, 1999, pp.21, 47~52
- Schindler CW, "Series introduction. JAK-STAT signaling in human disease", J Clin Invest, 109, pp.1133~1137 (2002)