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, V Taneja, A Bashmakov, S Nukala, Y Ye, J Orme, D Sajitharan, H-Y Kim, C Mohan
Index: Clin. Exp. Immunol. 172(2) , 217-27, (2013)
Full Text: HTML
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.© 2013 British Society for Immunology.
Related Compounds
Related Articles:
2014-04-01
[J. Surg. Res. 187(2) , 542-52, (2014)]
2013-01-09
[J. Ethnopharmacol. 145(1) , 311-9, (2013)]
2014-01-01
[J. Neurosci. 34(1) , 10-21, (2014)]
2013-10-01
[Open Biol. 3(10) , 130021, (2013)]
2013-05-01
[Diabetes 62(5) , 1537-46, (2013)]