Ankylosing spondylitis M-CSF-derived macrophages are undergoing unfolded protein response (UPR) and express higher levels of interleukin-23

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 unfo...

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Bibliographic Details
Published in:Modern rheumatology 2017-09, Vol.27 (5), p.862-867
Main Authors: Rezaiemanesh, Alireza, Mahmoudi, Mahdi, Amirzargar, Ali Akbar, Vojdanian, Mahdi, Jamshidi, Ahmad Reza, Nicknam, Mohammad Hossein
Format: Article
Language:English
Subjects:
Adult
Ankylosing spondylitis
Apoptosis
Female
HLA-B27
HLA-B27 Antigen - metabolism
Humans
Interleukin-17 - metabolism
Interleukin-23
Interleukin-23 - metabolism
Macrophage
Macrophage Colony-Stimulating Factor - metabolism
Macrophages - metabolism
Macrophages - pathology
Male
Middle Aged
Monocytes - metabolism
Monocytes - pathology
Spondylitis, Ankylosing - immunology
Spondylitis, Ankylosing - metabolism
Unfolded protein response (UPR)
Unfolded Protein Response - physiology
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Summary: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.
ISSN:1439-7595
1439-7609
DOI:10.1080/14397595.2016.1259716