Systemic lupus erythematosus is associated with impaired autophagic degradation via interleukin-6 in macrophages.
Biochim Biophys Acta Mol Basis Dis
; 1867(2): 166027, 2021 02 01.
Article
em En
| MEDLINE
| ID: mdl-33248276
ABSTRACT
Systemic lupus erythematosus (SLE) is an autoimmune disease associated with dysregulated interleukin (IL)-6 and autophagy. Although such disturbances are increasingly recognized in patients with SLE and animal models of the disease, little is known about the specific role of IL-6 and autophagy in SLE macrophages. Here, we investigated alterations in the IL-6 axis and autophagy in macrophages derived from patients with SLE and determined whether IL-6 modulates autophagy using human macrophage models. Serum IL-6 detected by ELISA was higher in SLE patients (n = 19) than in normal controls (n = 19, p < 0.001). Levels of the IL-6 receptor (IL-6R) and autophagic markers LC3B and p62 in SLE and normal macrophages were assessed by real-time PCR, western blotting, and immunofluorescence. Compared with normal macrophages, SLE macrophages not only overexpressed IL-6Rs but also exhibited impaired autophagic degradation as evidenced by elevated levels of LC3B and p62. In vitro analyses using macrophage models revealed that prolonged exposure to exogenous recombinant human IL-6 induced a marked impairment of autophagic degradation indicated by elevated levels of LC3B and p62 in both primary macrophages and transformed macrophages. Pretreatment with tocilizumab, a humanized anti-IL-6R monoclonal antibody, restored autophagic degradation and reversed p62 accumulation in a paracrine manner in macrophages. These findings demonstrate that SLE involves IL-6-induced impairment of autophagic degradation through augmentation of IL-6R in human macrophages.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autofagia
/
Interleucina-6
/
Receptores de Interleucina-6
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Lúpus Eritematoso Sistêmico
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Macrófagos
Tipo de estudo:
Diagnostic_studies
/
Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Biochim Biophys Acta Mol Basis Dis
Ano de publicação:
2021
Tipo de documento:
Article