PMID- 12842758
OWN - NLM
STAT- MEDLINE
DCOM- 20040312
LR  - 20191107
IS  - 1043-4666 (Print)
IS  - 1043-4666 (Linking)
VI  - 22
IP  - 5
DP  - 2003 Jun 7
TI  - Ligation of IFN-gamma-induced HLA-DR molecules on fibroblasts induces RANTES 
      expression via c-Jun N-terminal kinase (JNK) pathway.
PG  - 107-15
AB  - 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-alpha 
      (TNF-alpha)-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.
FAU - Meguro, Michio
AU  - Meguro M
AD  - Department of Patho-physiology/Periodontal Science, Okayama University Graduate 
      School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8525, Japan.
FAU - Nishimura, Fusanori
AU  - Nishimura F
FAU - Ohyama, Hideki
AU  - Ohyama H
FAU - Takashiba, Shogo
AU  - Takashiba S
FAU - Murayama, Yoji
AU  - Murayama Y
FAU - Matsushita, Sho
AU  - Matsushita S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Cytokine
JT  - Cytokine
JID - 9005353
RN  - 0 (Chemokine CCL5)
RN  - 0 (HLA-DR Antigens)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Chemokine CCL5/genetics/*metabolism
MH  - Enzyme Activation
MH  - Fibroblasts/*metabolism
MH  - HLA-DR Antigens/*metabolism
MH  - Humans
MH  - Interferon-gamma/metabolism
MH  - JNK Mitogen-Activated Protein Kinases
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Phosphorylation
MH  - *Signal Transduction
EDAT- 2003/07/05 05:00
MHDA- 2004/03/16 05:00
CRDT- 2003/07/05 05:00
PHST- 2003/07/05 05:00 [pubmed]
PHST- 2004/03/16 05:00 [medline]
PHST- 2003/07/05 05:00 [entrez]
AID - S1043466603001236 [pii]
AID - 10.1016/s1043-4666(03)00123-6 [doi]
PST - ppublish
SO  - Cytokine. 2003 Jun 7;22(5):107-15. doi: 10.1016/s1043-4666(03)00123-6.