Systemic lupus erythematosus is associated with impaired autophagic degradation via interleukin-6 in macrophages

Hui Ching Hsu, Yu Hsuan Chen, Tin Syuan Lin, Chieh Yu Shen, Song Chou Hsieh

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

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.

Original languageEnglish
Article number166027
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1867
Issue number2
DOIs
Publication statusPublished - Feb 2021

Keywords

  • IL-6/IL-6R axis
  • Impairment of autophagic degradation
  • Macrophages
  • Systemic lupus erythematosus
  • Tocilizumab

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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