Auranofin inhibits overproduction of pro-inflammatory cytokines, cyclooxygenase expression and PGE2 production in macrophages

Abstract

Auranofin (AF), a gold compound, is an orally active therapeutic agent used to treat rheumatoid arthritis (RA), a self-perpetuating inflammatory disease. RA is characterized by autoimmune-mediated proliferation of synovial cells that leads to inflammation, pain, and swelling in most major joints: However, the mechanism as to how AF relieves RA symptoms has not been fully elucidated. The object of this study was to examine the ability of AF to immunomodulate macrophages as antigen presenting cells (APCs). Macrophages are recognized as playing an important role in the pathogenesis of RA, in that there is a relative abundance of macrophage-derived cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) in rheumatoid synovium. In this work, we tested whether AF (2.5-20 mM) could inhibit inflammatory activity in the macrophage cell line RAW 264.7. AF decreased production of nitric oxide (NO) and the pro-inflammatory cytokines, TNF-alpha, IL-1beta and IL-6 in macrophages. Furthermore, AF inhibited cyclooxygenase-2 (COX-2)-dependent prostaglandin E2 (PGE2) production in a concentration-dependent manner. In conclusion, these findings may provide an explanation for the clinical effects of AF in patients with RA.

Nicotine Augments Glomerular Injury in a Rat Model of Acute Nephritis

“…It has been observed both clinically and experimentally that the expression and activity of COX-2 was significantly upregulated in inflammatory conditions, including several forms of nephritis [20, 21]. The effects of nicotine on glomerular cell count (documented above) suggested to us that, in the setting of nephritis, nicotine may have a proinflammatory effect.…”

Human Serum Albumin-Delivered [Au(PEt3)]+ Is a Potent Inhibitor of T Cell Proliferation

“…These include lysosomal and extracellular cathepsin proteases involved in antigen processing and matrix degradation in diseased tissues, respectively. 4,5 Gold(I) complexes, especially those bearing lipophilic phosphine (PR 3 ) ligands, have also shown potent antiproliferative activity in cancer cell lines and antitumor activity in vivo. Auranofin (Chart 1) is currently being evaluated for the treatment of chronic lymphocytic leukemia (CLL) in phase II clinical trials.…”

Microscopic Analysis of the Interaction of Gold Nanoparticles with Cells of the Innate Immune System

“…However there is still much to know about their mechanisms of action 2 and new methods to study their interactions with cells of the immune system are highly desirable. A novel way to study the role of gold and its interaction with the immune system could be to use AuNPs, since their path can be easily followed and they can be visualized using electron microscopy methods.…”