Document Type : Original Article

Authors

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

¹ DepartmentofBiology, Central Tehran Branch, Islamic Azad University, Tehran, Iran.

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

³ Rheumatology Research Center, Tehran University of Medical Sciences, Tehran Iran. Inflammation Research Center, Tehran University of Medical Sciences, Tehran, Iran.

⁴ Department of Biostatistics, School ofHealth, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Abstract

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), this study aimed to assess the mRNA expression pattern of genes involved in the
UPR pathway in macrophages from smoker and non-smoker BD patients. This case-control study was conducted between 2015
and 2016 in Shariati Hospital, Tehran, Iran. Monocytes were enriched from obtained whole blood samples of 10 smokers and 10
non-smoker BD patients as well as 10 healthy individuals. Using 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. Among the measured genes, HERP mRNA was overexpressed in macrophages from BD
patients in comparison with healthy macrophages. HERP and GADD34 genes were upregulated in smoker BD patients compared
with non-smoker BD patients as well as healthy subjects. Cigarette smoke can induce UPR gene expression in BD patients. The
altered UPR gene expression in BD macrophages may contribute to BD pathogenesis.

Keywords

• Behcet’s syndrome
• macrophages
• unfolded protein response

Main Subjects

• Behest's Disease