The role of chemokines and adhesion molecules in the pathogenesis of rheumatoid arthritis.

Rheumatoid arthritis (RA) is characterized by marked infiltration of the synovium by T-cells. The mediator of joint inflammation has been shown to be both cellular and soluble and the concept of cross-talk between adhesion molecules and cytokines, and its relevance to inflammation, is emerging. The expression and function of adhesion molecules are tightly regulated via intracellular signaling induced by cytokine or chemokine stimulation, a process which is designated "inside-to-out signaling". Such regulation is particularly important in inflammatory processes in which T-cells migrate from the circulation into the tissue. Adhesion molecules not only function as glue, but also transduce extracellular information into cytoplasmic organelles via the "outside-to-in signal", resulting in cell activation and cytokine production. For instance, the abundant intracellular adhesion molecule ICAM-1 and CD44 on RA synoviocytes not only potentially facilitate the interaction with T-cells or extracellular matrix, but also induce cytokine gene transcription in synovial cells. Thus, the two-directional cross-talk among adhesion molecules and cytokines appears to be significant for the initiation and prolongation of inflammatory processes through T-cell migration into RA synovial tissues and activation of both T-cells and synovial cells in this region. The concept proposed would greatly help in clarifying the pathological processes in rheumatoid synovitis, as well as in discovering new pharmacological approaches to more specifically control synovial inflammation. (c) 2001 Prous Science. All rights reserved.