title: Modulation of Wnt5a expression by periodontopathic bacteria.
abstract: Wingless proteins, termed Wnt, are involved in embryonic development, blood cell differentiation, and tumorigenesis. In mammalian hematopoiesis, Wnt signaling is essential for stem-cell homeostasis and lymphocyte differentiation. Recent studies have suggested that these molecules are associated with cardiovascular diseases, rheumatoid arthritis, and osteoarthritis. Furthermore, Wnt5a signaling is essential for the general inflammatory response of human macrophages. Periodontitis is a chronic inflammatory disease caused by gram-negative periodontopathic bacteria and the resultant host immune response. Periodontitis is characterized by loss of tooth-supporting structures and alveolar bone resorption. There have been no previous reports on Wnt5a expression in periodontitis tissue, and only few study reported the molecular mechanisms of Wnt5a expression in LPS-stimulated monocytic cells. Using RT-PCR, we demonstrated that Wnt5a mRNA expression was up-regulated in chronic periodontitis tissue as compared to healthy control tissue. P. gingivalis LPS induced Wnt5a mRNA in the human monocytic cell line THP-1 with a peak at 4 hrs after stimulation. P. gingivalis LPS induced higher up-regulation of Wnt5a mRNA than E. coli LPS. The LPS receptors TLR2 and TLR4 were equally expressed on the surface of THP-1 cells. P. gingivalis LPS induced IκBα degradation and was able to increase the NF-κB binding activity to DNA. P. gingivalis LPS-induced Wnt5a expression was inhibited by NF-κB inhibitors, suggesting NF-κB involvement. Furthermore, IFN-γ synergistically enhanced the P. gingivalis LPS-induced production of Wnt5a. Pharmacological investigation and siRNA experiments showed that STAT1 was important for P. gingivalis LPS-induced Wnt5a expression. These results suggest that the modulation of Wnt5a expression by P. gingivalis may play an important role in the periodontal inflammatory process and serve a target for the development of new therapies.
authors.affiliation: Department of Periodontology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Nanbara
authors.forename: Nawarat
authors.initials: N
authors.lastname: Wara-aswapati
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Nagasawa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Reiko
authors.initials: R
authors.lastname: Yashiro
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Bando
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Janjura
authors.initials: J
authors.lastname: Khongcharoensuk
authors.forename: Doosadee
authors.initials: D
authors.lastname: Hormdee
authors.forename: Waranuch
authors.initials: W
authors.lastname: Pitiphat
authors.forename: Jason A
authors.initials: JA
authors.lastname: Boch
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Izumi
mesh_terms: D000293:Adolescent; D000328:Adult; D016866:Bacteroidaceae Infections / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation; D005881:Gingiva / Q000378:metabolism* / Q000382:microbiology; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology; D053612:Janus Kinases / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010518:Periodontitis / Q000378:metabolism* / Q000382:microbiology; D016966:Porphyromonas gingivalis; D061251:Primary Cell Culture; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D015854:Up-Regulation; D051153:Wnt Proteins / Q000235:genetics* / Q000378:metabolism; D000071818:Wnt-5a Protein; D055815:Young Adult
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D050791:STAT Transcription Factors; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D007371:Interferon-gamma; D053612:Janus Kinases