TRAIL mRNA expression in peripheral blood mononuclear cells of Egyptian SLE patients Safaa Mostafa El-Karaksy a , Naglaa Mohamed Kholoussi b , Rasha Mohamad Hosny Shahin a, ⁎, Mona Mohsen Abou El-Ghar b , Rasha El-Sayed Gheith c a Department of Clinical Pathology, Kasr El Aini Hospital, Cairo University, Cairo, Egypt b Department of Clinical Pathology, National Research Institute, Cairo, Egypt c Department of Rheumatology and Rehabilitation, Kasr El Aini Hospital, Cairo University, Cairo, Egypt abstract article info Article history: Accepted 24 May 2013 Available online 18 June 2013 Keywords: Systemic lupus erythematosus Tumor-necrosis factor-related apoptosis- inducing ligand (TRAIL) Real-time reverse transcription-polymerase chain reaction Although the definite etiopathogenesis of systemic lupus erythematosus (SLE) remains unclear, many different mechanisms may contribute to its pathogenesis. Tumor-necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor (TNF) family with pro-apoptotic activity. The accumulation of apoptotic cell debris has been hypothesized to induce the autoimmune inflammation in SLE, and TRAIL may trigger this programmed cell death. We investigated TRAIL mRNA expression levels in peripheral blood mono- nuclear cells (PBMCs) from 60 SLE patients and 40 controls using quantitative real-time reverse transcription- polymerase chain reaction (RT-PCR), and we studied the association between the results and clinical and labora- tory parameters of the patients. Expression levels of TRAIL mRNAs in SLE patients were significantly higher than in controls (p b 0.001). A statistically significant association was detected between TRAIL mRNA expression and SLE activity (p = 0.001). © 2013 Elsevier B.V. All rights reserved. 1. Introduction Systemic lupus erythematosus (SLE) is an autoimmune disease with a broad spectrum of clinical and immunological abnormalities. The etiology of the disease remains unknown. There is, however, increasing evidence that the presence and accumulation of apoptotic cells play a role in autoimmunity (White and Rosen, 2003). Dying cells serve as potential reservoirs of modified forms of autoantigens that may trigger autoantibody responses in susceptible individuals (Kaplan, 2004). Increased neutrophil, monocyte, and lymphocyte apoptosis is a characteristic feature of SLE pathophysiology (Ren et al., 2003). Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), which is also known as apoptosis ligand 2 (Apo2L), is a member of TNF family of cytokines, which are structurally related proteins playing important roles in regulating cell death, immune response, and inflammation (Nomura et al., 2007). Like most other members of the TNF superfamily of ligands, TRAIL is expressed as a type II membrane protein of about 33–35 kDa on surfaces of the cells, which are mostly in immune system, including T lymphocytes, monocytes, dendritic cells, natural killer (NK) cells, and neutrophils (Wei et al., 2005). While similar to other membrane-bound ligands of the TNF super- family, TRAIL can be processed by cysteine proteases and soluble TRAIL is present at relatively high levels in the culture supernatant of activated peripheral blood mononuclear cells (PBMCs) (Liabakk et al., 2002). In humans, TRAIL interacts with five different receptors. Two agonistic receptors, DR4 (death receptor 4 or TRAIL-R1) and DR5 (death receptor 5, TRAIL-R2), are capable of transmitting a death signal, whereas the remaining three receptors, DcR1 (decoy receptor 1, TRAIL-R3) and DcR2 (decoy receptor 2, TRAIL-R4), and the soluble receptor, osteoprotegerin, act as decoy receptors blocking TRAIL-induced apoptosis (Truneh et al., 2000). TRAIL has a well-recognized role in mediating apoptosis not only of malignant cells, but also of monocytes, neutrophils, plas- ma cells, as well as normal and HIV-infected lymphocytes (Rus et al., 2005). Additionally, TRAIL also exerts some proinflammatory effects, e.g. the induction of interleukin-8 and intercellular adhesion molecule- 1. In lupus nephritis, TRAIL is strongly expressed in the proximal tubular epithelial cells, and promotes local inflammation (Nguyen et al., 2009). Gene 527 (2013) 211–214 Abbreviations: ANAs, antinuclear antibodies; Apo2L, apoptosis ligand 2; C3, complement; CBC, complete blood count; DcR1, decoy receptor 1; DR4, death receptor 4; dsDNA, double-stranded deoxyribonucleic acid antibodies; ESR, erythrocyte sedimentation rate; GAPDH, glyceraldehydes-3-phosphate dehydrogenase; IFN, interferon; mRNA, messenger RNA; NK, natural killer; PBMCs, peripheral blood mononu- clear cells; RT-PCR, real-time reverse transcription-polymerase chain reaction; SLE, systemic lupus erythematosus; SLEDAI, systemic lupus erythematosus disease activity index; TNF, tumor necrosis factor; TRAIL, Tumor necrosis factor-related apoptosis- inducing ligand. ⁎ Corresponding author at: 11c, Street 199, Apt. # 9, Degla, Maadi, Cairo 11431, Egypt. Tel.: +20 1005142041. E-mail address: rachachahine@yahoo.com (R.M.H. Shahin). 0378-1119/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.gene.2013.05.084 Contents lists available at SciVerse ScienceDirect Gene journal homepage: www.elsevier.com/locate/gene