Impaired Macrophage Autophagy Exerted by Interleukin-6 and its Implication in Systemic Lupus Erythematosus
Date Issued
2016
Date
2016
Author(s)
Hsu, Hui-Ching
Abstract
Background: Autophagy is a condition by which cells break down their own components to maintain homeostasis. Autophagy, initially viewed as a bulk-degradation mechanism in adaption to harsh environment, has been found to play a crucial role in immunity and inflammation. It has been proposed that defect in clearance of apoptotic cell debris and aberrant antigen presentation might be the link between autophagy and systemic lupus erythematosus (SLE). During apoptosis, nuclear proteins can be modified and redistributed on the cell surface. Under physiological conditions, these proteins are rapidly removed by macrophages and do not induce any autoimmunity. Therefore impaired macrophage function is also implicated in SLE. Interleukin-6 (IL-6) is a multifunctional cytokine, which plays a critical role in B cell hyperactivity and immunopathology of human SLE. The connection between impaired macrophage autophagy and SLE pathogenesis remains unclear. Here, we investigate the role of IL-6 in autophagy of macrophage. Methods: THP-1 cell line derived macrophages and primary human monocyte-derived macrophages were treated with IL-6 and IL-6 receptor antagonist (IL-6 RA). We detected autophagy function by LC3-II turnover assay and p62 level using Western blots. Results: Impaired autophagy of THP-1 macrophages after IL-6 treatment was demonstrated by elevated LC3-II and p62 on Western blots. Using rapamycin as positive control of autophagy, the results were consistent. After pre-treatment with IL-6 receptor antagonist, the effects of IL-6 on macrophage autophagy can be reversed. Similar results were seen on primary human monocyte-derived macrophages. Monocyte-derived macrophages of a SLE patient with arthritis and pyuria also showed impaired autophagy. The role of IL-6 in macrophage autophagy in SLE will be discussed.
Subjects
Autophagy
macrophages
systemic lupus erythematosus
IL-6
Type
thesis
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