Kelley James M, Hughes Laura B, Bridges S Louis
Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
J Neuroinflammation. 2008 Jan 3;5:1. doi: 10.1186/1742-2094-5-1.
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.
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.
近期研究表明，脊髓p38丝裂原活化蛋白激酶（MAPK）在慢性炎症和外周关节炎的发展中起作用，γ-氨基丁酸（GABA）在抑制p38 MAPK介导的效应中起作用。综合这些数据表明，GABA可能在下调导致促炎因子如白细胞介素-1、白细胞介素-6和基质金属蛋白酶3产生的机制中发挥作用，这些因子与类风湿性关节炎（RA）的发病机制有关。遗传学研究也将RA与p38 MAPK途径的成员联系起来。
我们提出一个假设，即GABA信号系统效率低下，导致通过p38 MAPK途径不受控制地产生促炎细胞因子。该模型还支持增加免疫与神经科学整合研究的必要性。
