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Tytuł pozycji:

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

Tytuł:
Systemic lupus erythematosus is associated with impaired autophagic degradation via interleukin-6 in macrophages.
Autorzy:
Hsu HC; Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Chen YH; Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Lin TS; Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan; Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
Shen CY; Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
Hsieh SC; Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: .
Źródło:
Biochimica et biophysica acta. Molecular basis of disease [Biochim Biophys Acta Mol Basis Dis] 2021 Feb 01; Vol. 1867 (2), pp. 166027. Date of Electronic Publication: 2020 Nov 25.
Typ publikacji:
Journal Article; Observational Study; Research Support, Non-U.S. Gov't
Język:
English
Imprint Name(s):
Original Publication: Amsterdam : Elsevier
MeSH Terms:
Autophagy/*immunology
Interleukin-6/*metabolism
Lupus Erythematosus, Systemic/*immunology
Macrophages/*metabolism
Receptors, Interleukin-6/*metabolism
Antibodies, Monoclonal, Humanized/pharmacology ; Antibodies, Monoclonal, Humanized/therapeutic use ; Autophagy/drug effects ; Case-Control Studies ; Cells, Cultured ; Healthy Volunteers ; Humans ; Interleukin-6/blood ; Lupus Erythematosus, Systemic/blood ; Lupus Erythematosus, Systemic/diagnosis ; Lupus Erythematosus, Systemic/drug therapy ; Macrophages/immunology ; Microtubule-Associated Proteins/analysis ; Microtubule-Associated Proteins/metabolism ; Paracrine Communication/drug effects ; Paracrine Communication/immunology ; Primary Cell Culture ; RNA-Binding Proteins/analysis ; RNA-Binding Proteins/metabolism ; Receptors, Interleukin-6/analysis ; Receptors, Interleukin-6/antagonists & inhibitors ; Recombinant Proteins/metabolism ; Severity of Illness Index ; THP-1 Cells
Contributed Indexing:
Keywords: IL-6/IL-6R axis; Impairment of autophagic degradation; Macrophages; Systemic lupus erythematosus; Tocilizumab
Substance Nomenclature:
0 (Antibodies, Monoclonal, Humanized)
0 (IL6 protein, human)
0 (IL6R protein, human)
0 (Interleukin-6)
0 (MAP1LC3B protein, human)
0 (Microtubule-Associated Proteins)
0 (P62 protein, human)
0 (RNA-Binding Proteins)
0 (Receptors, Interleukin-6)
0 (Recombinant Proteins)
I031V2H011 (tocilizumab)
Entry Date(s):
Date Created: 20201128 Date Completed: 20210423 Latest Revision: 20210423
Update Code:
20240105
DOI:
10.1016/j.bbadis.2020.166027
PMID:
33248276
Czasopismo naukowe
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.
(Copyright © 2020 Elsevier B.V. All rights reserved.)

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