Mice Producing Less Reactive Oxygen Species Are Relatively Resistant to Collagen Glycopeptide Vaccination against Arthritis

Batsalova, Tsvetelina; Dzhambazov, Balik; Klaczkowska, Dorota; Holmdahl, Rikard

doi:10.4049/jimmunol.1000385

Cited by 10 publications

(9 citation statements)

References 57 publications

(62 reference statements)

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“…28 days prior to CIA immunisation, decreased severity and frequency of arthritis [ 30 ]. Since most protocols for induction of tolerance in CIA have been performed using repeated administrations of antigen to achieve a treatment effect [ 26 , 35 ], it is striking that a single injection of tolerogenic lentiviral particles rendered a substantial amelioration of arthritis particularly when given at days 7 or 26 after CII immunisation. This is in line with the study by Dzhambazov et al which showed that vaccination with the CII epitope complexed with soluble A q molecules has both prophylactic and therapeutic effects in a model of chronic CIA [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Antigen-Specific Gene Therapy after Immunisation Reduces the Severity of Collagen-Induced Arthritis

Eneljung

Tengvall

Jirholt

et al. 2013

Clinical and Developmental Immunology

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Reestablishment of tolerance induction in rheumatoid arthritis (RA) would be an optimal treatment with few, if any, side effects. However, to develop such a treatment further insights in the immunological mechanisms governing tolerance are needed. We have developed a model of antigen-specific tolerance in collagen type II (CII) induced arthritis (CIA) using lentivirus-based gene therapy. The immunodominant epitope of CII was inserted into a lentivirus vector to achieve expression on the MHC class II molecule and the lentiviral particles were subsequently intravenously injected at different time points during CIA. Injection of lentiviral particles in early phases of CIA, that is, at day 7 or day 26 after CII immunisation, partially prevented development of arthritis, decreased the serum levels of CII-specific IgG antibodies, and enhanced the suppressive function of CII-specific T regulatory cells. When lentiviral particles were injected during manifest arthritis, that is, at day 31 after CII immunisation, the severity of arthritis progression was ameliorated, the levels of CII-specific IgG antibodies decreased and the proportion of T regulatory cells increased. Thus, antigen-specific gene therapy is effective when administered throughout the inflammatory course of arthritis and offers a good model for investigation of the basic mechanisms during tolerance in CIA.

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Section: Discussionmentioning

confidence: 99%

Antigen-Specific Gene Therapy after Immunisation Reduces the Severity of Collagen-Induced Arthritis

Eneljung

Tengvall

Jirholt

et al. 2013

Clinical and Developmental Immunology

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“…Phoxinduced ROS causes oxidative tissue damage through lipid and protein oxidation in several disease models. [16][17][18][19][20][21][22] However, data from mice and humans indicate that ROS may also downregulate inflammation by not yet fully understood processes. [23][24][25][26] In fact, failure to terminate the inflammation may provide a central mechanism for nonresolving inflammatory disease, including ANCA vasculitis.…”

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confidence: 99%

Phagocyte NADPH Oxidase Restrains the Inflammasome in ANCA-Induced GN

Schreiber

Luft

Kettritz

2015

Journal of the American Society of Nephrology

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ANCA-activated phagocytes cause vasculitis and necrotizing crescentic GN (NCGN). ANCA-induced phagocyte NADPH oxidase (Phox) may contribute by generating tissue-damaging reactive oxygen species. We tested an alternative hypothesis, in which Phox restrains inflammation by downregulating caspase-1, thereby reducing IL-1b generation and limiting NCGN. In an antimyeloperoxidase (anti-MPO) antibody-mediated disease model, mice transplanted with either gp91 phox -deficient or p47 phox -deficient bone marrow showed accelerated disease with increased crescents, necrosis, glomerular monocytes, and renal IL-1b levels compared with mice transplanted with wild-type bone marrow. IL-1b receptor blockade abrogated aggravated NCGN in gp91 phox -deficient mice. In vitro, challenge with anti-MPO antibody strongly enhanced caspase-1 activity and IL-1b generation in gp91 phox -deficient and p47 phox -deficient monocytes compared with wild-type monocytes. This enhanced IL-1b generation was abrogated when caspase-1 was blocked. ANCA-induced superoxide and IL-1b generation were inversely related in human monocytes. Furthermore, transplantation of gp91 phox /caspase-1 double-deficient bone marrow rescued the accelerated NCGN phenotype in gp91 phox bone marrow-deficient mice. These results suggest that Phox-generated reactive oxygen species downregulate caspase-1, thereby keeping the inflammasome in check and limiting ANCA-induced inflammation. IL-1 receptor blockade may provide a promising strategy in NCGN, whereas our data question the benefit of antioxidants.

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“…Damaged antioxidant system of the body will result in excessive aggregation of ROS and its relevant metabolites. As a result, it will lead to tissue injury, cognitive defect, emotional disorder and multiple other diseases (13). It is indicated in research that oxidative stress is positively correlated with RA.…”

Section: Discussionmentioning

confidence: 99%

Effect of Scutellarin inhibits collagen-induced arthritis through TLR4/NF-κB-mediated inflammation

Zhang

et al. 2017

Molecular Medicine Reports

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Scutellarin is the major effective constituent of the commonly used Chinese medicine Erigeron breviscapus. It has been applied in the clinic to treat various diseases, and is characterized by high content, a stable source, controllable quality, high efficiency and low toxicity. In addition, its potential pharmacological effects have been increasingly identified and elucidated. The present study was performed to examine the role of scutellarin on collagen‑induced arthritis (CIA). Mice were injected subcutaneously with bovine collagen type II and administered scutellarin for 2 weeks by gavage 20 mg/kg/day. ELISA kits were used to measure the levels of interleukin (IL)‑1β, IL‑6, tumor necrosis factor‑α (TNF‑α), oxidative stress markers [superoxide dismutase (SOD) and malondialdehyde (MDA)] and caspase‑3/-9 activity. Bax, Bcl‑2, toll like receptor 4 (TLR4) and nuclear factor (NF)‑κB protein expression was analyzed using western immunoblot analyses. The present study demonstrated that scutellarin prevented CIA, and inhibited the expression of inflammation factors, IL‑1β, IL‑6 and TNF‑α. In addition, scutellarin reduced the levels of oxidative stress markers, SOD and MDA, as well as intercellular adhesion molecule‑1 and monocyte chemoattractant protein 1 in CIA mice. Caspase‑3/-9, Bax/Bcl‑2, TLR4 and NF‑κB protein expression were reduced in CIA mice following scutellarin treatment. The results of the current study suggest a novel effect of scutellarin involving the inhibition of TLR4/NF‑κB‑mediated inflammation.

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Mice Producing Less Reactive Oxygen Species Are Relatively Resistant to Collagen Glycopeptide Vaccination against Arthritis

Cited by 10 publications

References 57 publications

Antigen-Specific Gene Therapy after Immunisation Reduces the Severity of Collagen-Induced Arthritis

Antigen-Specific Gene Therapy after Immunisation Reduces the Severity of Collagen-Induced Arthritis

Phagocyte NADPH Oxidase Restrains the Inflammasome in ANCA-Induced GN

Effect of Scutellarin inhibits collagen-induced arthritis through TLR4/NF-κB-mediated inflammation

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