Ligation of IFN-γ-induced HLA-DR molecules on fibroblasts induces RANTES expression via c-Jun N-terminal kinase (JNK) pathway

Michio Meguro, Fusanori Nishimura, Hideki Ohyama, Shogo Takashiba, Yoji Murayama, Sho Matsushita

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The role of human leukocyte antigen (HLA) class II molecules on non-antigen presenting cells has been a matter of controversy. We recently reported that ligation of HLA-DR molecule with anti-HLA-DR antibodies (L243) and/or antigenic peptide/T cell receptor complex resulted in a secretion of several chemokines such as RANTES. In the present study, we aimed to detect putative signal transduction pathway leading to RANTES production from fibroblasts when the DR molecules were ligated with L243. Protein tyrosine kinase inhibitor (GF109203X) suppressed RANTES expression in a dose dependent manner for up to 50% from gingival fibroblasts (GF), while protein kinase C inhibitor (genistein) had no inhibitory effect. Ligation of DR molecules with L243 resulted in tyrosine phosphorylation of 54 kDa cellular protein. Thus, we suspected that either Jun N-terminal kinase-2 (JNK-2) or Src family proteins were involved in HLA-DR-mediated signaling. JNK inhibitor (SP600125), but not Src inhibitor (PP2), suppressed both L243 stimulated RANTES mRNA expression and protein secretion. The maximum inhibition for RANTES production by SP600125 was more than 80%. Additionally, JNK inhibitor nearly completely blocked tumor necrosis factor-α (TNF-α)-induced RANTES production in GF. Furthermore, ligation of GF HLA-DR with L243 induced selective phosphorylation of JNK-2. We concluded that JNK-2 was one of the HLA-DR-mediated signal transduction pathways.

Original languageEnglish
Pages (from-to)107-115
Number of pages9
JournalCytokine
Volume22
Issue number5
DOIs
Publication statusPublished - Jun 7 2003

Fingerprint

Chemokine CCL5
JNK Mitogen-Activated Protein Kinases
Fibroblasts
HLA Antigens
Ligation
Molecules
Mitogen-Activated Protein Kinase 9
Signal transduction
Phosphorylation
Protein Kinase Inhibitors
Signal Transduction
Peptide T
Proteins
Protein C Inhibitor
Genistein
T-Cell Antigen Receptor
Chemokines
Protein-Tyrosine Kinases
Protein Kinase C
Tyrosine

Keywords

  • Fibroblasts
  • HLA-DR molecule
  • Jun N-terminal kinase-2
  • RANTES

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology
  • Immunology
  • Immunology and Allergy

Cite this

Ligation of IFN-γ-induced HLA-DR molecules on fibroblasts induces RANTES expression via c-Jun N-terminal kinase (JNK) pathway. / Meguro, Michio; Nishimura, Fusanori; Ohyama, Hideki; Takashiba, Shogo; Murayama, Yoji; Matsushita, Sho.

In: Cytokine, Vol. 22, No. 5, 07.06.2003, p. 107-115.

Research output: Contribution to journalArticle

Meguro, Michio ; Nishimura, Fusanori ; Ohyama, Hideki ; Takashiba, Shogo ; Murayama, Yoji ; Matsushita, Sho. / Ligation of IFN-γ-induced HLA-DR molecules on fibroblasts induces RANTES expression via c-Jun N-terminal kinase (JNK) pathway. In: Cytokine. 2003 ; Vol. 22, No. 5. pp. 107-115.
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