Intra-articular nuclear factor-κB blockade ameliorates collagen-induced arthritis in mice by eliciting regulatory T cells and macrophages

S. Y. Min, M. Yan, Y. Du, T. Wu, E. Khobahy, S. R. Kwon, Veena D Taneja, A. Bashmakov, S. Nukala, Y. Ye, J. Orme, D. Sajitharan, H. Y. Kim, C. Mohan

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Abstract

Nuclear factor (NF)-κB is a transcription factor implicated in the pathogenesis of autoimmune disorders such as rheumatoid arthritis (RA). Here we have examined the effect of intra-articular administration of the IKK inhibitor, NEMO-binding domain peptide (NBD), on the severity of collagen-induced arthritis (CIA). NBD peptides were injected intra-articularly into the knee joints of DBA/1J mice after the onset of disease. Collagen-injected mice given a scrambled peptide served as controls. Arthritis severity was determined by visual examination of paws. Intra-articular NBD injection reduced the arthritis score and ameliorated morphological signs of bone destruction compared to the controls. Serum levels of type-II collagen-specific immunoglobulin (Ig)G2a antibodies were lower in NBD-treated mice versus the control mice, whereas the levels of type-II collagen-specific IgG1 antibodies were increased by NBD treatment. NBD treatment diminished the proinflammatory cytokines interleukin (IL)-17 and interferon (IFN)-γ in serum, but increased the regulatory cytokine IL-10. NBD-treated CIA mice exhibited significantly higher percentages and numbers of forkhead box protein 3 (FoxP3+)CD4+CD25+ regulatory T cells than controls. Immunofluorescence analysis of NBD-treated mice revealed that FoxP3 and Ym1, a marker of alternatively activated macrophages, were juxtaposed to each other within draining inguinal lymph nodes. Intra-articular administration of NBD peptide is effective as an experimental therapy in a murine model of RA. Nevertheless, the intra-articular treatment modality is still associated with systemic effects on the immune system.

Original languageEnglish (US)
Pages (from-to)217-227
Number of pages11
JournalClinical and Experimental Immunology
Volume172
Issue number2
DOIs
StatePublished - May 2013

Fingerprint

Experimental Arthritis
Regulatory T-Lymphocytes
Joints
Macrophages
Collagen Type II
Peptides
Arthritis
Rheumatoid Arthritis
Cytokines
Forkhead Transcription Factors
Inbred DBA Mouse
Investigational Therapies
Interleukin-17
Antibodies
Groin
Knee Joint
Protein Domains
Serum
Interleukin-10
Interferons

Keywords

  • Alternatively activated macrophages
  • Autoimmunity
  • Collagen-induced arthritis
  • NBD peptide
  • Regulatory T cells

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Intra-articular nuclear factor-κB blockade ameliorates collagen-induced arthritis in mice by eliciting regulatory T cells and macrophages. / Min, S. Y.; Yan, M.; Du, Y.; Wu, T.; Khobahy, E.; Kwon, S. R.; Taneja, Veena D; Bashmakov, A.; Nukala, S.; Ye, Y.; Orme, J.; Sajitharan, D.; Kim, H. Y.; Mohan, C.

In: Clinical and Experimental Immunology, Vol. 172, No. 2, 05.2013, p. 217-227.

Research output: Contribution to journalArticle

Min, SY, Yan, M, Du, Y, Wu, T, Khobahy, E, Kwon, SR, Taneja, VD, Bashmakov, A, Nukala, S, Ye, Y, Orme, J, Sajitharan, D, Kim, HY & Mohan, C 2013, 'Intra-articular nuclear factor-κB blockade ameliorates collagen-induced arthritis in mice by eliciting regulatory T cells and macrophages', Clinical and Experimental Immunology, vol. 172, no. 2, pp. 217-227. https://doi.org/10.1111/cei.12054
Min, S. Y. ; Yan, M. ; Du, Y. ; Wu, T. ; Khobahy, E. ; Kwon, S. R. ; Taneja, Veena D ; Bashmakov, A. ; Nukala, S. ; Ye, Y. ; Orme, J. ; Sajitharan, D. ; Kim, H. Y. ; Mohan, C. / Intra-articular nuclear factor-κB blockade ameliorates collagen-induced arthritis in mice by eliciting regulatory T cells and macrophages. In: Clinical and Experimental Immunology. 2013 ; Vol. 172, No. 2. pp. 217-227.
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AU - Taneja, Veena D

AU - Bashmakov, A.

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AU - Ye, Y.

AU - Orme, J.

AU - Sajitharan, D.

AU - Kim, H. Y.

AU - Mohan, C.

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