FIGURE 2 

Feedback loops in NF-B signaling. IKK may be activated by the TNF signaling pathway as well as the MyD88-dependent arm of the LPS signaling pathway. IKK leads to NF-B activity, which is regulated by a negative feedback loop involving IB (described in detail in Box 1), as depicted in the lower center. TNF-induced NF-B activity also leads to A20 expression, and subsequent decrease in IKK activation. Also, the Trif-dependent arm of the LPS-signaling pathway activates the transcription factor interferon regulatory factor-3 (IRF3), leading to TNF expression and subsequent autocrine signaling. Thus, A20 and TNF form feedback loops that regulate NF-B activity.