Upregulation of pro-inflammatory cytokines could also modulate NF-κb activation through positive feedback, thereby, a vicious loop is formed, which intensifies RA development.272,273 At the same time, excessive NF-κB activation also induces apoptosis of abnormal FLS cells in RA.274 In the RA synovium inflammatory microenvironment, aberrant apoptosis of FLS is the major factor associated with RA synovium hyperplasia. Here, NFKB1 is linked to rheumatoid arthritis.