Figure 4.

Regulation of the hypoxia-inducible factor-1α (HIF-1α) and nuclear factor-κB (NF-κB) pathways by reactive oxygen species (ROS) and cytokine stimulation. The complex and interrelated activation of these two critical transcription factors is central to most of the processes that sustain synovitis in rheumatoid arthritis, such as endothelial activation, leukocyte recruitment, angiogenesis, and enhanced cell survival. IL, interleukin; MAPK, mitogen-activated protein kinase; PI3K, phosphoinositide 3-kinase; TNF, tumor necrosis factor.