Impact of rheumatoid arthritis-associated HLA-DRbeta1 subtypes on protein kinase A signaling

Chin Med J (Engl). 2003 May;116(5):712-6.

Abstract

Objective: To investigate the impact of rheumatoid arthritis (RA)-associated HLA-DRbeta1 * 0401, * 0402, * 0403, * 0404 and * 0101 subtypes on the protein kinase A (PKA) signaling pathway.

Methods: Adenylate cyclase (AC), cAMP and PKA activity in transfectants expressing RA-associated HLA-DRbeta1 subtypes and their mutants were detected.

Results: Compared to HLA-DRbeta1 * 0402 transfectants, the RA-associated HLA-DRbeta1 * 0401, * 0404 and * 0101 transfectants produced significantly lower levels of AC, cAMP and PKA.

Conclusion: RA-associated HLA-DRbeta1 molecules are involved in the pathogenesis of RA through down-regulation of the PKA signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclases / analysis
  • Arthritis, Rheumatoid / etiology
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / immunology*
  • Cyclic AMP / analysis
  • Cyclic AMP / genetics
  • Cyclic AMP-Dependent Protein Kinases / physiology*
  • Down-Regulation
  • HLA-DR Antigens / analysis
  • HLA-DR Antigens / genetics*
  • Immunophenotyping
  • In Vitro Techniques
  • Signal Transduction*

Substances

  • HLA-DR Antigens
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Adenylyl Cyclases