title: Does gamma-aminobutyric acid (GABA) influence the development of chronic inflammation in rheumatoid arthritis?
abstract: BACKGROUND
  Recent studies have demonstrated a role for spinal p38 MAP kinase (MAPK) in the development of chronic inflammation and peripheral arthritis and a role for GABA in the inhibition of p38 MAPK mediated effects. Integrating these data suggests that GABA may play a role in downregulating mechanisms that lead to the production of proinflammatory agents such as interleukin-1, interleukin-6, and matrix metalloproteinase 3 - agents implicated in the pathogenesis of rheumatoid arthritis (RA). Genetic studies have also associated RA with members of the p38 MAPK pathway.
  
  
  OBJECTIVE
  We propose a hypothesis for an inefficient GABA signaling system that results in unchecked proinflammatory cytokine production via the p38 MAPK pathway. This model also supports the need for increasing research in the integration of immunology and neuroscience.
authors.affiliation: Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA. jmkelley@uab.edu
authors.forename: James M
authors.initials: JM
authors.lastname: Kelley
authors.forename: Laura B
authors.initials: LB
authors.lastname: Hughes
authors.forename: S Louis
authors.initials: SL
authors.lastname: Bridges
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D007375:Interleukin-1; D015850:Interleukin-6; D005680:gamma-Aminobutyric Acid; D048051:p38 Mitogen-Activated Protein Kinases; D019278:Matrix Metalloproteinase 3