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Clin Exp Immunol ; 172(2): 217-27, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23574318

RESUMO

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.


Assuntos
Artrite Experimental/tratamento farmacológico , Artrite Experimental/imunologia , Macrófagos/imunologia , NF-kappa B/antagonistas & inibidores , Linfócitos T Reguladores/imunologia , Animais , Artrite Experimental/metabolismo , Autoimunidade , Antígenos CD4/biossíntese , Colágeno , Fatores de Transcrição Forkhead/biossíntese , Imunoglobulina G/imunologia , Interferon gama/sangue , Interleucina-10/sangue , Interleucina-17/biossíntese , Subunidade alfa de Receptor de Interleucina-2/biossíntese , Lectinas , Ativação Linfocitária , Ativação de Macrófagos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos DBA , Peptídeos/administração & dosagem , Peptídeos/farmacologia , Linfócitos T Reguladores/metabolismo , beta-N-Acetil-Hexosaminidases
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