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

Xin You, Meng Pan, Wenli Gao, Her Shyong Shiah, Jian Tao, Dongqing Zhang, Fotios Koumpouras, Shuang Wang, Hongyu Zhao, Joseph A. Madri, David Baker, Yung Chi Cheng, Zhinan Yin

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Objective. 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. Methods. 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 α (TNFα) and interleuldn-1β (IL-1β) 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. Results. 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 macrophages examined ex vivo. Treatment also reduced the levels of inflammatory cytokines (EL-6, IL-12, TNFα, and monocyte chemotactic protein 1) produced by bone marrow-derived dendritic cells in vitro. However, DCB 3503 showed no direct effects on T cell proliferation and B cell antibody response. Conclusion. Because of its ability to specifically suppress innate immune responses, DCB 3503 may be a novel therapeutic agent for inflammatory arthritis in humans.

Original languageEnglish
Pages (from-to)877-886
Number of pages10
JournalArthritis and Rheumatism
Volume54
Issue number3
DOIs
Publication statusPublished - Mar 1 2006
Externally publishedYes

Fingerprint

Experimental Arthritis
Innate Immunity
Joints
Cytokines
Lipopolysaccharides
Dendritic Cells
Arthritis
Tumor Necrosis Factor-alpha
Bone Marrow
tylophorine
DCB 3503
Inbred DBA Mouse
Collagen Type II
Chemokine CCL2
Interleukin-12
Antibody Formation
Flow Cytometry
B-Lymphocytes
Therapeutics
Enzyme-Linked Immunosorbent Assay

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

Cite this

Effects of a novel tylophorine analog on collagen-induced arthritis through inhibition of the innate immune response. / You, Xin; Pan, Meng; Gao, Wenli; Shiah, Her Shyong; Tao, Jian; Zhang, Dongqing; Koumpouras, Fotios; Wang, Shuang; Zhao, Hongyu; Madri, Joseph A.; Baker, David; Cheng, Yung Chi; Yin, Zhinan.

In: Arthritis and Rheumatism, Vol. 54, No. 3, 01.03.2006, p. 877-886.

Research output: Contribution to journalArticle

You, X, Pan, M, Gao, W, Shiah, HS, Tao, J, Zhang, D, Koumpouras, F, Wang, S, Zhao, H, Madri, JA, Baker, D, Cheng, YC & Yin, Z 2006, 'Effects of a novel tylophorine analog on collagen-induced arthritis through inhibition of the innate immune response', Arthritis and Rheumatism, vol. 54, no. 3, pp. 877-886. https://doi.org/10.1002/art.21640
You, Xin ; Pan, Meng ; Gao, Wenli ; Shiah, Her Shyong ; Tao, Jian ; Zhang, Dongqing ; Koumpouras, Fotios ; Wang, Shuang ; Zhao, Hongyu ; Madri, Joseph A. ; Baker, David ; Cheng, Yung Chi ; Yin, Zhinan. / Effects of a novel tylophorine analog on collagen-induced arthritis through inhibition of the innate immune response. In: Arthritis and Rheumatism. 2006 ; Vol. 54, No. 3. pp. 877-886.
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abstract = "Objective. 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. Methods. 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 α (TNFα) and interleuldn-1β (IL-1β) 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. Results. 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 macrophages examined ex vivo. Treatment also reduced the levels of inflammatory cytokines (EL-6, IL-12, TNFα, and monocyte chemotactic protein 1) produced by bone marrow-derived dendritic cells in vitro. However, DCB 3503 showed no direct effects on T cell proliferation and B cell antibody response. Conclusion. Because of its ability to specifically suppress innate immune responses, DCB 3503 may be a novel therapeutic agent for inflammatory arthritis in humans.",
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AU - Zhang, Dongqing

AU - Koumpouras, Fotios

AU - Wang, Shuang

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AU - Cheng, Yung Chi

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AB - Objective. 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. Methods. 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 α (TNFα) and interleuldn-1β (IL-1β) 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. Results. 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 macrophages examined ex vivo. Treatment also reduced the levels of inflammatory cytokines (EL-6, IL-12, TNFα, and monocyte chemotactic protein 1) produced by bone marrow-derived dendritic cells in vitro. However, DCB 3503 showed no direct effects on T cell proliferation and B cell antibody response. Conclusion. Because of its ability to specifically suppress innate immune responses, DCB 3503 may be a novel therapeutic agent for inflammatory arthritis in humans.

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