TNF and rheumatoid arthritis: In addition, studies on synovial tissue specimens from RA patients and cultures of human rheumatoid fibroblast-like synoviocytes demonstrated that melatonin exerts anti-inflammatory activities by downregulating TNF-α and IL-1 production via suppression of PI3K/AKT, ERK, and NF-κB signaling and upregulation of miR-3150a-3p (a microRNA) expression, in an MT1 receptor-dependent manner [89].