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

• Published in: Modern rheumatology Vol. 27; no. 5; pp. 862 - 867
• Main Authors: Rezaiemanesh, Alireza, Mahmoudi, Mahdi, Amirzargar, Ali Akbar, Vojdanian, Mahdi, Jamshidi, Ahmad Reza, Nicknam, Mohammad Hossein
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 03.09.2017
• 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; HLA-B27; Interleukin-23; Ankylosing spondylitis; Macrophage; Unfolded protein response (UPR)
• ISSN: 1439-7595; 1439-7609
• DOI: 10.1080/14397595.2016.1259716

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.