Table 2.

Functions of the key molecular mediators associated with the pathogenesis of RA

Molecular mediators	Function	Reference
Signaling molecules
ERK	Production of proinflammatory cytokines and MMPs, lymphocyte activation and differentiation	117–119, 121, 122, 124, 125
P38	Release of proinflammatory cytokines, COX-2 and MMPs	127, 128
JNK	Expression of cytokines, growth factors, cell surface receptors, cell adhesion molecules and MMPs	135
Nuclear factors
NF-kB	Expression of cytokines (TNF-α, IL-1β, IL-6, IL-6, IL-17, IFN-γ, etc.), chemokines (MCP-1, MCP-4, CCL18, etc.), adhesion molecules (E-selectin, ICAM-1, VCAM-1, etc.), MMPs, VEGF, NOS and COX	141
AP-1	Activation of cytokine production, T-cell differentiation, interaction with and trans-repression of the glucocorticoid receptor, and MMP expression	149–151

COX- cyclooxygenase, ICAM- intracellular adhesion molecule, IFN- interferon, IL- interleukin, MCP- monocyte chemoattractant protein, MMPs- matrix metalloproteases, NOS- inducible nitric oxide synthase, TNF- tumor necrosis factor, VCAM- vascular cell adhesion molecule and VEGF- vascular endothelial growth factor.