Downregulation of Autophagy-related Genes in Macrophages from Patients with Behcet's Disease

Abstract

Objective: Overwhelming inflammatory chemokines and cytokines characterize the immunological profile and inflammatory settings of Behcet disease (BD). The connection between autophagy-related genes (ATGs) and various perspectives of innate and adaptive immunobiology such as antigen presentation, immune tolerance, lymphocyte development and differentiation, cytokine signaling, and inflammation have been implicated. The aim of this study was to evaluate the mRNA expression profile of ATGs in macrophages of patients with BD. Materials and Methods: Whole blood samples were obtained from 10 BD patients and 10 healthy controls. Monocytes were isolated from the blood samples and then differentiated to macrophages using macrophage colony-stimulating factor (M-CSF). After total RNA extraction and cDNA synthesis, quantitative analysis of ATGs including ATG5, ATG7, ATG12, LC3b, mTOR, RAPTOR, and RICTOR was conducted by SYBR Green master mix and real-time polymerase chain reaction (PCR). Results: mRNA expression of all ATGs was downregulated in macrophages of BD patients compared with healthy controls. It is worth to note that the downregulation of ATG12 and LC3b mRNAs in macrophages of BD patients was statistically significant in comparison to that of healthy control group (P = 0.007 and 0.021, respectively). Conclusion: Considering the role of autophagy in initiation of immune responses and then clearance of dead cells as well as its participation in the development and differentiation of immune cells, downregulation of ATGs in macrophages of BD patients may be involved in uncontrolled immune response and overproduction of inflammatory cytokines.

Keywords

• Behcet disease
• Autophagy-related genes
• Macrophage
• Inflammation