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Role of CTA1R7K-COL...
Role of CTA1R7K-COL-DD as a novel therapeutic mucosal tolerance-inducing vector for treatment of collagen-induced arthritis.
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- Hasselberg, Annemarie, 1973 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology
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- Schön, Karin, 1962 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology
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- Tarkowski, Andrej, 1951 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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- Lycke, Nils Y, 1954 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology
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(creator_code:org_t)
- Wiley, 2009
- 2009
- Engelska.
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Ingår i: Arthritis and rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 60:6, s. 1672-82
- Relaterad länk:
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https://onlinelibrar...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- OBJECTIVE: To determine whether a cholera toxin-derived, novel immunomodulating fusion protein, CTA1R7K-COL-DD, carrying the class II major histocompatibility complex H-2q-restricted type II collagen peptide aa 259-274, can induce therapeutic tolerance and prevent collagen-induced arthritis (CIA) when administered intranasally in DBA/1 mice, and to assess whether ADP-ribosylation at the mucosal membranes exerts a regulatory function such that the outcome of tolerance or immune enhancement can be controlled. METHODS: DBA/1 mice with CIA were treated intranasally with CTA1R7K-COL-DD. The therapeutic effect was monitored for 46 days after the onset of disease. Clinical scoring of disease, histologic examination of inflammation, and bone erosion were assessed, and cytokine levels were determined in the serum or supernatants from splenocytes stimulated with recall antigen. RESULTS: The protective effect of CTA1R7K-COL-DD resulted in roughly 60% of the mice having no clinical signs or histologic evidence of disease after treatment, and those with CIA had significantly milder disease with less bone erosion. The protective status was associated with lower serum titers of IgG1, IgG2a, IgG2b, and IgG3 anticollagen and a substantial decrease in the production of interleukin-6 (IL-6), IL-17, and interferon-gamma, while levels of IL-10 were markedly up-regulated both in the serum and at the T cell level. CONCLUSION: The enzymatically inactive mutant fusion protein CTA1R7K-COL-DD provided substantial therapeutic protection against CIA following intranasal administration. The mechanism behind the effect appears to be mediated by peptide-specific regulatory T cells induced by mucosal exposure to the peptide containing CTA1R7K-COL-DD vector. In addition, ADP-ribosylation at the mucosal membranes acts as a key regulator controlling mucosal tolerance or immunity.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
Nyckelord
- ADP Ribose Transferases
- metabolism
- Administration
- Intranasal
- Animals
- Arthritis
- Experimental
- chemically induced
- metabolism
- prevention & control
- CD4-Positive T-Lymphocytes
- metabolism
- Cholera Toxin
- administration & dosage
- genetics
- therapeutic use
- Disease Models
- Animal
- Drug Tolerance
- physiology
- Immunoglobulin G
- metabolism
- Interleukin-10
- metabolism
- Interleukin-17
- metabolism
- Interleukin-6
- metabolism
- Male
- Mice
- Mice
- Inbred DBA
- Mucous Membrane
- metabolism
- Peptide Fragments
- genetics
- physiology
- therapeutic use
- Plasmids
- Recombinant Fusion Proteins
- administration & dosage
- genetics
- therapeutic use
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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