Alpha-melanocyte stimulating hormone ameliorates disease activity in an induced murine lupus-like model

Autor(es)

Botte, D. A. C. ^[1] ; Noronha, I. L. ^[2] ; Malheiros, D. M. A. C. ^[2] ; Peixoto, T. V. ^[1] ; de Mello, S. B. V. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med, Dept Internal Med, BR-01246903 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Fac Med, Dept Internal Med, Div Nephrol, BR-01246903 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: CLINICAL AND EXPERIMENTAL IMMUNOLOGY; v. 177, n. 2, p. 381-390, AUG 2014.
• Citações Web of Science: 10

Resumo

Alpha-melanocyte stimulating hormone (alpha-MSH) is a neuropeptide exhibiting anti-inflammatory activity in experimental models of autoimmune diseases. However, no studies thus far have examined the effects of alpha-MSH on systemic lupus erythematosus (SLE). This study aimed to determine the effects of an alpha-MSH agonist in induced murine lupus. Here we employed female Balb/cAn mice in which lupus was induced by pristane. Groups of lupus animals were treated daily with the alpha-MSH analogue {[}Nle4, DPhe7]-alpha-MSH (NDP-MSH) (1 25 mg/kg) injected intraperitoneally or saline for 180 days. Normal animals comprised the control group. Arthritis incidence, plasma immunoglobulin (Ig)G isotypes, anti-nuclear antibodies (ANA) and plasma cytokines were evaluated. Renal function was assessed by proteinuria and histopathological lesion. Glomerular levels of IgG, alpha-smooth muscle actin (alpha-SMA), inducible nitric oxide synthase (iNOS), C3, CD3, melanocortin receptors (MCR)1, corticotrophin-releasing factor (CRF) and alpha-MSH was estimated by immunohistochemistry. When compared with normal controls, lupus animals exhibited increased arthritis, IgG levels, ANA, interleukin (IL)-6, IL-10, proteinuria and mesangial cell proliferation together with glomerular expression of alpha-SMA and iNOS. Glomerular expression of MCR1 was reduced in lupus animals. NDP-MSH treatment reduced arthritis scores by 70% and also diminished IgG1 and IgG2a levels and ANA incidence. In the glomerulus, NDP-MSH treatment reduced cellularity by 50% together with reducing IgG deposits, and expression levels of alpha-SMA, iNOS and CRF were also all decreased. Taken together, our results suggest for the first time that alpha-MSH treatment improves several parameters of SLE disease activity in mice, and indicate that this hormone is an interesting potential future treatment option. (AU)

• Processo FAPESP: 09/54549-8 - Avaliação do efeito antiinflamatório do hormônio estimulador de melanócito (alfa ±MS)H no lúpus eritematoso sistêmico: estudo experimental e em humanos
• Beneficiário: Suzana Beatriz Verissimo de Mello
• Modalidade de apoio: Auxílio à Pesquisa - Regular