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Intracellular Signal Transduction in Oral Keratinocytes and Infiltrated Lymphocytes Obtained from Patients with Oral Lichen Planus-Biochemical Analysis of the Mechanism of Enhanced Cytokine Generation from Keratinocytes and Infiltration of Lymphocytes

Research Project

Project/Area Number 08457499
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 病態科学系歯学(含放射線系歯学)
Research InstitutionKochi Medical School

Principal Investigator

YAMAMOTO Tetsuya  Kochi Medical School, Department of Oral Surgery, Assistant Professor, 医学部附属病院, 講師 (00200824)

Co-Investigator(Kenkyū-buntansha) UETA Eisaku  Kochi Medical School, Department of Oral Surgery, Research Associate, 医学部附属病院, 助手 (10203431)
YONEDA Kazunori  Kochi Medical School, Department of Oral Surgery, Associate Professor, 医学部, 助教授 (90182849)
OSAKI Tokio  Kochi Medical School, Department of Oral Surgery, Professor, 医学部, 教授 (70031995)
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥6,200,000 (Direct Cost: ¥6,200,000)
Fiscal Year 1998: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1996: ¥2,500,000 (Direct Cost: ¥2,500,000)
Keywordsoral lichen planus / keratinocytes / beta_1 and beta_2 integrins / mononulcear leukocytes / cytokine / nuclear factor (NF)-_KB / lipopolysaccharide (LPS) / CD59 / migration / 接着因子 / チロシンリン酸化 / 細胞内シグナル伝達
Research Abstract

By immunobiological examination in oral lichen planus (OLP), we obtained following results.
1) Compared with oral keratinocytes (KC) obtained from the intact oral mucosae, KC from patients with OLP (OLP-KC) generaled larger amounts of GM-CSF, lL-6, TNF-alpha and 1L-1beta.
2) Cytokines generated from OLP-KC enhanced chemotaxis of peripheral blood mononulcear cells (PBMC) and they increased migration of PBMC through monolayered blood vessel endothelial cells.
3) Supernatants of OLP-KC activated PBMC, upregulating PKC activity, 1P_3 and [Ca^<2+>]i levels and protein tyrosine phosphorylation.
4) Correspondingly. adhesion molecules such as CD11a, CD11b, and CD18 and CD49d on PBMC and their counterparts ICAM-1. VCAM-l and ELAM-I on endothelial cells were more expressed by supernatants of OLP-KC and the enhanced migration of PBMC depended on the expression of these adhesion molecules.
5) Cytokine generation by I{C was not. enhanced by metal ions but enhanced by E.coli-LPS and heat (42゚C) and heat shock protein (65 kDa) peptide.
6) The enhanced cytokine generation from KC was associated with PKC activation, protein tyrosine phosphorylation and NV-KB activation.
7) CD14 was not. expressed on KC and activation of KC by LPS was mediated by CD59.
These results indicate that cytokines generated from KC induce migration of PBMC through expression of adhesion molecules and that exaggeration of cytokine generation from KC may be induced by extrinsic stimulant such as heat and UPS.Specification of the stimulant in each patient with OLP and the role of infiltrated PBMC in the impairment of the basal cells remain to be clarified in the future.

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (3 results)

All Other

All Publications (3 results)

  • [Publications] 山本哲也: "口腔扁平苔癬における単核球の浸潤機序に関する生物学的検討" 日本口腔科学会雑誌. 48・1. 10-14 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tetsuya Yamamoto: "Biological study on mechanism of mononuclear cell infiltration in oral lichen planus" Journal of Japanese Stomatological Society. 48. 10-14 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 山本 哲也: "口腔扁平苔癬における単核球の浸潤機序に関する生物学的検討" 日本口腔科学会雑誌 (印刷中). 印刷中. (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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