In both TNF-α-induced fibroblast-like synoviocytes and LPS or IFN-γ-treated monocytic cell lines (U937), nicotine (0.1, 1, and 10 μM) inhibited cell proliferation and reduced the expression of MMP9 and VEGF, indicating that nicotine played a crucial protective role in pannus formation and joint destruction in rheumatoid arthritis (61). This evidence concerns the gene TNF and rheumatoid arthritis.