Document Type : Original Article

Authors

• Maliheh Heshmatpanah ¹
• Nakisa Zarrabi Ahrabi ¹
• Farhad Shahram ²
• Maassoumeh Akhlaghi ³
• Maryam Akhtari ⁴
• Elmira Shamsian ⁴
• Shayan Mostafaee ⁵
• Mahdi Mahmoudi ⁶

¹ Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran

² Professor of Rheumatology, Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran

³ Rheumatology Research Center, Shariati hospital, Tehran University of Medical Sciences, Tehran, Iran

⁴ Rheumatology Research Center, Tehran University of Medical Sciences, Tehran Iran

⁵ Department of Biostatistics, School of Health, Kermanshah University of Medical Sciences, Kermanshah, Iran.‎

⁶ Rheumatology Research Center, Tehran University of Medical Sciences

Abstract

Background: Endoplasmic reticulum (ER) stress triggers the unfolded protein response (UPR), ‎which has been correlated with enhanced production of inflammatory cytokines. Given the ‎important pathogenic roles of macrophages and inflammatory responses in the etiopathogenesis ‎of Behcet’s disease (BD), here we tried to assess the mRNA expression pattern of genes ‎involved in the UPR pathway in macrophages from smoker and non-smoker BD patients.‎
Methods: This case-control study was conducted between 2015 and 2016 in Shariati Hospital, ‎Tehran, Iran. In this study, monocytes were enriched from obtained whole blood samples of 10 ‎smoker and 10 non-smoker BD patients as well as 10 healthy individuals. Using the ‎macrophage-colony stimulating factor (M-CSF), separated monocytes were differentiated into ‎macrophages. After total RNA purification and cDNA synthesis, quantification analysis of UPR ‎genes, including activating transcription factor (ATF) 4, ATF6, X-box binding protein 1 ‎‎(XBP1), Binding immunoglobulin protein (BIP), C/EBP homologous protein (CHOP), ‎homocysteine-inducible, endoplasmic reticulum stress-inducible, ubiquitin-like domain member ‎‎1 (HERP), and growth arrest and DNA damage-inducible protein (GADD34), was performed ‎using SYBR green master mix and real-time PCR.‎
Results: Among the measured genes, HERP mRNA was overexpressed in macrophages from ‎BD patients in comparison to healthy macrophages. HERP and GADD34 genes were ‎upregulated in smoker BD patients in comparison to non-smoker BD patients as well as healthy ‎subjects.‎
Conclusions: Cigarette smoke can induce UPR gene expression in BD patients. The altered ‎UPR gene expression in BD macrophages may contribute to the BD pathogenesis. ‎

Keywords

• Behcet syndrome, Macrophages, Unfolded protein response.&lrm

Main Subjects

• Behest's Disease