1. Ankylosing spondylitis M-CSF-derived macrophages are undergoing unfolded protein response (UPR) and express higher levels of interleukin-23.
- Author
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Rezaiemanesh A, Mahmoudi M, Amirzargar AA, Vojdanian M, Jamshidi AR, and Nicknam MH
- Subjects
- Adult, Apoptosis, Female, HLA-B27 Antigen metabolism, Humans, Interleukin-17 metabolism, Macrophage Colony-Stimulating Factor metabolism, Male, Middle Aged, Monocytes metabolism, Monocytes pathology, Unfolded Protein Response physiology, Interleukin-23 metabolism, Macrophages metabolism, Macrophages pathology, Spondylitis, Ankylosing immunology, Spondylitis, Ankylosing metabolism
- Abstract
Objective: Interleukin (IL)-23/IL-17 pathway involves in the pathogenesis of ankylosing spondylitis (AS). The exact mechanism implicated in overexpression of IL-23 and activation of the IL-23/IL-17 axis is not clear. The aim of the study was to clarify whether macrophages of AS patients undergo unfolded protein response (UPR) and secret increased IL-23., Methods: Peripheral blood monocyte isolated from 10 HLA-B27
+ patients and five HLA-B27+ normal subjects were differentiated to macrophages by macrophage-colony stimulating factor (M-CSF) for seven days. Flow cytometry was used to detect monocyte purity and expression of macrophage markers. Analysis of mRNA expression for HLA-B and B27, UPR-associated proteins (BiP, CHOP, MDG1, and XBP1) and IL-23 was performed by RT-qPCR., Results: RT-qPCR data showed a significant overexpression of HLA-B27, UPR genes (BiP, CHOP, and XBP1), and IL-23 in M-CSF-derived macrophages from AS patients compared to healthy controls. Increased expression of MDG1 was not significant., Conclusions: Our data suggest that UPR activation occurs in M-CSF-derived macrophages of AS patients and is accompanied by overexpression of HLA-B27. UPR appears to be associated with overproduction of IL-23 in AS macrophages.- Published
- 2017
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