In the present study, we provide evidence that in the arthritic microenvironment of the joints, TNFR1 signaling downstream of TNF and independently of IL-1β can induce Mir221/222 levels in SFs apart from LPS and could suggest that increased TNF and IL-1β levels can serve as signals that lead to Mir221/222 upregulation specifically in RA SFs. Here, TNF is linked to rheumatoid arthritis.