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 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.
['Rezaiemanesh|Alireza|A|', 'Mahmoudi|Mahdi|M|', 'Amirzargar|Ali Akbar|AA|', 'Vojdanian|Mahdi|M|', 'Jamshidi|Ahmad Reza|AR|', 'Nicknam|Mohammad Hossein|MH|']
D000328:Adult D017209:Apoptosis D005260:Female D015796:HLA-B27 Antigen D006801:Humans D020381:Interleukin-17 D053759:Interleukin-23 D016173:Macrophage Colony-Stimulating Factor D008264:Macrophages D008297:Male D008875:Middle Aged D009000:Monocytes D013167:Spondylitis, Ankylosing D056811:Unfolded Protein Response
Ankylosing spondylitis Macrophage Unfolded protein response (UPR) Interleukin-23 HLA-B27