However, excessive immune responses can lead to autoimmune diseases, such as the activation of most TLRs induces NF-κB and AP-1 pathways.[51] Melittin inhibits TLR2 and TLR4 signaling pathways and is an effective treatment for RA.[16] AGEs binding to its receptor RAGE can cause intracellular oxidative stress, lead to NF-κB activation, further stimulating the production of growth factors and cytokines. This evidence concerns the gene TLR4 and rheumatoid arthritis.