Attenuation of Collagen-Induced Arthritis in Mice by Salmon Proteoglycan

Rheumatoid arthritis (RA) is a serious autoimmune disease caused by chronic inflammation of connective tissues. The basic principle of RA treatment is aimed to reduce joint inflammation. Our previous studies demonstrated that salmon cartilage proteoglycan (PG) suppresses excess inflammation in different mouse inflammatory diseases. In this study, we investigated the prophylactic effect of PG on the progression of RA using an experimental mouse model, collagen-induced arthritis (CIA). Clinical and histological severity of CIA was attenuated by daily oral administration of PG. In the joints of PG-administered mice, infiltration of macrophages and neutrophils and also osteoclast accumulation were limited. In comparison to nonadministered mice, anti-collagen antibodies in the sera of PG-administered mice did not alter. On the other hand, local expression of interleukin-17A (IL-17A), IL-6, IL-1β, interferon-γ(IFN-γ), C-C chemokine ligand 2 (CCL2), C-X-C chemokine ligand 1 (CXCL1), and CXCL2 in the joints of PG-administered mice decreased. Moreover, in the response of type II collagen- (CII-) restimulation ex vivo, IL-17A and IFN-γproduction by splenocytes from PG-administered mice was less than that of control mice. These data suggested that daily ingested PG attenuated CIA pathogenesis by modulating immune response of splenocytes to CII stimulation and local production inflammatory cytokines and chemokines in the joints.

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IL-10-Deficient B10.Q Mice Develop More Severe Collagen-Induced Arthritis, but Are Protected from Arthritis Induced with Anti-Type II Collagen Antibodies

The Journal of Immunology ◽

10.4049/jimmunol.167.6.3505 ◽

2001 ◽

Vol 167 (6) ◽

pp. 3505-3512 ◽

Cited By ~ 70

Author(s):

Åsa C. M. Johansson ◽

Ann-Sofie Hansson ◽

Kutty S. Nandakumar ◽

Johan Bäcklund ◽

Rikard Holmdahl

Keyword(s):

Type Ii Collagen ◽

Type Ii ◽

Collagen Induced Arthritis ◽

Collagen Antibodies

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Potent Antiarthritic Properties of Phloretin in Murine Collagen-Induced Arthritis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2016/9831263 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 9

Author(s):

Shun-Ping Wang ◽

Shih-Chao Lin ◽

Shiming Li ◽

Ya-Hsuan Chao ◽

Guang-Yuh Hwang ◽

...

Keyword(s):

Clinical Symptoms ◽

Bone Destruction ◽

Joint Inflammation ◽

Flavonoid Compound ◽

Therapeutic Effects ◽

Potential Candidate ◽

Collagen Induced Arthritis ◽

Hind Limbs ◽

Collagen Antibodies ◽

Anti Inflammatory

In the exploration of potential therapeutic agents for rheumatoid arthritis (RA), DBA/1J mice are used as the RA model of collagen-induced arthritis (CIA). Phloretin, a flavonoid compound extracted fromPrunus mandshurica, has been found to exhibit anti-inflammatory activity, making it a potential candidate for treatment of RA. The objective of this study was to evaluate the therapeutic effects of phloretin on CIA mice. CIA mice were dosed daily with phloretin at either 50 or 100 mg/kg among two treatment groups. CIA treated mice showed mitigation of clinical symptoms of RA in addition to reduced inflammation of hind-limbs compared to mice who did not receive phloretin. Histological analysis showed that phloretin suppressed the severity of RA and effectively mitigated joint inflammation and cartilage- and bone-destruction via reducing proinflammatory cytokine productions (TNF-α, IL-6, IL-1β, and IL-17). This was at least partially mediated by causing inadequate splenocyte activation and proliferation. Moreover, phloretin-treated CIA mice showed decreased oxidative stress and diminished levels of malondialdehyde (MDA) and hydrogen peroxide (H2O2) in paw tissues as well as reduced productivity of anti-collagen antibodies in serum. We have concluded that phloretin could be a potent and effective antiarthritis agent, demonstrating anti-inflammatory, antioxidative, and immunomodulatory effects in CIA mice.

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IL-10-Deficient B10.Q Mice Develop More Severe Collagen-Induced Arthritis, but Are Protected from Arthritis Induced with Anti-Type II Collagen Antibodies

The Journal of Immunology ◽

10.4049/jimmunol.169.10.6056 ◽

2002 ◽

Vol 169 (10) ◽

pp. 6056.1-6056

Author(s):

Åsa C. M. Johansson ◽

Ann-Sofie Hansson ◽

Kutty S. Nandakumar ◽

Johan Bäcklund ◽

Rikard Holmdahl

Keyword(s):

Type Ii Collagen ◽

Type Ii ◽

Collagen Induced Arthritis ◽

Collagen Antibodies

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MLN4924 protects against interleukin-17A-induced pulmonary inflammation by disrupting ACT1-mediated signaling

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00349.2018 ◽

2019 ◽

Vol 316 (6) ◽

pp. L1070-L1080 ◽

Cited By ~ 4

Author(s):

Rui Hao ◽

Yunduan Song ◽

Runsheng Li ◽

Yaxian Wu ◽

Xinyi Yang ◽

...

Keyword(s):

Inflammatory Response ◽

Proinflammatory Cytokines ◽

Inflammatory Diseases ◽

Pulmonary Inflammation ◽

Tumor Necrosis Factor Receptor ◽

Inhibitory Effect ◽

Chronic Obstructive ◽

Cytokines And Chemokines ◽

Interleukin 17A

An excessive inflammatory response in terminal airways, alveoli, and the lung interstitium eventually leads to pulmonary hypertension and chronic obstructive pulmonary disease. Proinflammatory cytokine interleukin-17A (IL-17A) has been implicated in the pathogenesis of pulmonary inflammatory diseases. MLN4924, an inhibitor of NEDD8-activating enzyme (NAE), is associated with the treatment of various types of cancers, but its role in the IL-17A-mediated inflammatory response has not been identified. Here, we report that MLN4924 can markedly reduce the expression of proinflammatory cytokines and chemokines such as IL-1β, IL-6, and CXCL-1 and neutrophilia in a mouse model of IL-17A adenovirus-induced pulmonary inflammation. MLN4924 significantly inhibited IL-17A-induced stabilization of mRNA of proinflammatory cytokines and chemokines in vitro. Mechanistically, MLN4924 significantly blocked the activation of MAPK and NF-κB pathways and interfered with the interaction between ACT1 and tumor necrosis factor receptor-associated factor proteins (TRAFs), thereby inhibiting TRAF6 ubiquitination. Taken together, our data uncover a previously uncharacterized inhibitory effect of MLN4924 on the IL-17A-mediated inflammatory response; this phenomenon may facilitate the development of MLN4924 into an effective small-molecule drug for the treatment of pulmonary inflammatory diseases.

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The impact of Clonorchis sinensis infection on immune response in mice with type II collagen-induced arthritis

10.21203/rs.2.17904/v1 ◽

2019 ◽

Author(s):

xiangyang li ◽

Ying Yang ◽

Su-Ping Qin ◽

Fan-Yun Kong ◽

Chao Yan ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Respiratory Exchange Ratio ◽

Clonorchis Sinensis ◽

Joint Inflammation ◽

Type Ii Collagen ◽

Type Ii ◽

Oral Gavage ◽

Collagen Induced Arthritis ◽

The Impact

Abstract Background Clonorchis sinensis infection could trigger strong immune responses in mice and human. However, whether the C.sinensis infection has an impact on arthritis is unknown. Here we investigated the effect of C.sinensis infection on type II collagen-induced arthritis in BALB/c mice.Results The mice were firstly infected with 45 C.sinensis metacercariae by oral gavage. Four weeks later, the arthritis in mice was induced by type II collagen. Joint inflammation with severe redness and swelling in hind paws were observed in type II collagen-induced arthritis (CIA) mice. In addition, the physical activity was significantly reduced, but the respiratory exchange ratio was increased in CIA mice. Compared with CIA mice, C.sinensis infection could increase the severity of arthritis in CIA mice, based on the results of disease score and pathological changes. Compared to CIA mice, increased neutrophils and Ly6C hi monocytes, decreased B cells and CD4+T cells were found in C.sinensis infected CIA mice. Besides these, C.sinensis infected mice also displayed significant higher levels of serum IL-4 and IL-17 than those in CIA mice. Taken together, our data suggest that C.sinensis infection have a bad effect on arthritis, and could induce the abnormality of immune response in mice with CIA.

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Type II collagen-induced arthritis in rats. Passive transfer with serum and evidence that IgG anticollagen antibodies can cause arthritis.

Journal of Experimental Medicine ◽

10.1084/jem.155.1.1 ◽

1982 ◽

Vol 155 (1) ◽

pp. 1-16 ◽

Cited By ~ 240

Author(s):

J M Stuart ◽

M A Cremer ◽

A S Townes ◽

A H Kang

Keyword(s):

Type Ii Collagen ◽

Passive Transfer ◽

Type Ii ◽

Autoimmune Process ◽

Collagen Induced Arthritis ◽

Collagen Antibodies ◽

Circulating Immune Complex ◽

Early Lesion ◽

Anticollagen Antibodies ◽

Bovine Type

We have found that serum from rats with type II collagen-induced arthritis, when fractionated with 50% ammonium sulfate and concentrated, would transfer arthritis to nonimmunized recipients. The arthritis in recipients developed within 18-72 h and displayed all of the major histopathologic characteristics of the early lesion in immunized animals but was transient and less severe. Although consideration was given to the possibility that a circulating immune complex was involved, no evidence of such a complex was detected. Further fractionation of the serum yielded an IgG anticollagen antibody that was fully active in transferring disease. The antibody's reaction was inhibited by the native bovine type II collagen used for immunization of donors and the antibody strongly cross-reacted with homologous type II collage but not with denatured collagen. These studies demonstrate that arthritis in rats can be induced with anti-type II collagen antibodies and suggest that an autoimmune process is involved. Because antibodies to collagen have also been detected in human rheumatic diseases, further investigation of the characteristics of collagen antibodies capable of inducing arthritis seems warranted.

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The impact of Clonorchis sinensis infection on immune response in mice with type II collagen-induced arthritis

10.21203/rs.2.17904/v2 ◽

2020 ◽

Author(s):

xiangyang li ◽

Ying Yang ◽

Su-Ping Qin ◽

Fan-Yun Kong ◽

Chao Yan ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Respiratory Exchange Ratio ◽

Clonorchis Sinensis ◽

Joint Inflammation ◽

Type Ii Collagen ◽

Type Ii ◽

Oral Gavage ◽

Collagen Induced Arthritis ◽

The Impact

Abstract Background: Clonorchis sinensis infection could trigger strong immune responses in mice and humans. However, whether the C.sinensis infection has an impact on arthritis is unknown. Here we investigated the effect of C.sinensis infection on type II collagen-induced arthritis in BALB/c mice. Results: The mice were firstly infected with 45 C.sinensis metacercariae by oral gavage. Four weeks later, arthritis in mice was induced by type II collagen. Joint inflammation with severe redness and swelling in hind paws was observed in type II collagen-induced arthritis (CIA) mice. Besides, the physical activity was significantly reduced, but the respiratory exchange ratio was increased in CIA mice. Compared with CIA mice, C.sinensis infection could increase the severity of arthritis in CIA mice, based on the results of disease score and pathological changes. Compared to CIA mice, increased neutrophils and Ly6Chi monocytes, decreased B cells and CD4+T cells, were found in C.sinensis infected CIA mice. Besides these, C.sinensis infected mice also displayed significantly higher levels of serum IL-4 and IL-17 than those in CIA mice. Conclusions: Taken together, our data suggest that C.sinensis infection have a bad effect on arthritis, and could induce the abnormality of the immune response in mice with CIA.

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The impact of Clonorchis sinensis infection on immune response in mice with type II collagen-induced arthritis

10.21203/rs.2.17904/v3 ◽

2020 ◽

Author(s):

xiangyang li ◽

Ying Yang ◽

Su-Ping Qin ◽

Fan-Yun Kong ◽

Chao Yan ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Respiratory Exchange Ratio ◽

Clonorchis Sinensis ◽

Joint Inflammation ◽

Type Ii Collagen ◽

Type Ii ◽

Oral Gavage ◽

Collagen Induced Arthritis ◽

The Impact

Abstract Background: Clonorchis sinensis infection could trigger strong immune responses in mice and humans. However, whether the C.sinensis infection has an impact on arthritis is unknown. Here we investigated the effect of C.sinensis infection on type II collagen-induced arthritis in BALB/c mice. Results: The mice were firstly infected with 45 C.sinensis metacercariae by oral gavage. Four weeks later, arthritis in mice was induced by type II collagen. Joint inflammation with severe redness and swelling in hind paws was observed in type II collagen-induced arthritis (CIA) mice. Besides, the physical activity was significantly reduced, but the respiratory exchange ratio was increased in CIA mice. Compared with CIA mice, C.sinensis infection could increase the severity of arthritis in CIA mice, based on the results of disease score and pathological changes. Compared to CIA mice, increased neutrophils and Ly6C hi monocytes, decreased B cells and CD4 + T cells, were found in C.sinensis infected CIA mice. Besides these, C.sinensis infected mice also displayed significantly higher levels of serum IL-4 and IL-17 than those in CIA mice. Conclusions: Taken together, our data suggest that C.sinensis infection have a bad effect on arthritis, and could induce the abnormality of the immune response in mice with CIA.

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