Effects of a novel tylophorine analog on collagen-induced arthritis through inhibition of the innate immune response

Arthritis and Rheumatism
Xin YouZhinan Yin

Abstract

To test the effects of a novel tylophorine analog, DCB 3503, on the prevention and treatment of collagen-induced arthritis (CIA) and to elucidate its underlying mechanisms. DBA/1J mice were immunized with type II collagen, and in some cases, lipopolysaccharide (LPS) was used to boost the development of arthritis. DCB 3503 was injected intraperitoneally before or after the onset of CIA. Mice were monitored to assess the effects of DCB 3503 on the clinical severity of the disease, and pathologic changes in the joints were examined histologically. Levels of tumor necrosis factor alpha (TNFalpha) and interleukin-1beta (IL-1beta) in serum and joint tissues were measured by enzyme-linked immunosorbent assay and by cytometric bead array analysis. The effect of DCB 3503 on LPS-induced proinflammatory cytokines from bone marrow-derived dendritic cells was determined by flow cytometry. DCB 3503 significantly suppressed the development and progression of CIA. Moreover, DCB 3503 completely blocked the LPS-triggered acceleration of joint inflammation and destruction. Consistent with its effects in vivo, DCB 3503 significantly suppressed the synthesis of proinflammatory cytokines in inflamed joints as well as cytokine synthesis by macrophage...Continue Reading

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Citations

Jan 17, 2013·Journal of Agricultural and Food Chemistry·Meng WuQingmin Wang
Apr 6, 2016·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·L Dinesh KumarT Sivasudha
Jan 21, 2014·Autoimmunity·Abdullah Alghasham, Zafar Rasheed
Jan 8, 2008·Seminars in Arthritis and Rheumatism·Shailesh R SatputeKamal D Moudgil
Sep 30, 2006·Arthritis and Rheumatism·Jin-Young ChoiJoseph Craft
Sep 16, 2014·ACS Medicinal Chemistry Letters·Ti WenQingmin Wang
May 29, 2007·Bioorganic & Medicinal Chemistry Letters·Wenli GaoYung-Chi Cheng
Dec 2, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Burtram C FieldingDamião Pergentino de Sousa
Oct 8, 2021·Biomolecules & Therapeutics·Chawon YunChoong Jae Lee

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