Differential upregulation of the hypothetical transmembrane protein 66 (TMEM66) in multiple sclerosis patients with potential inflammatory response

Abstract

The prevalence of multiple sclerosis (MS) in the Gulf region has markedly increased during the last decade, but the mechanisms of the disease have not been investigated. The present study aimed to understand the molecular processes involved in the disease development of the recently emerged MS in this population using microarray technology to investigate differentially-expressed novel genes in MS patients compared to healthy-matched subjects. The expression of the upregulated genes was confirmed by quantitative polymerase chain reaction (qPCR). Furthermore, gene cloning, protein expression and purification were performed followed by testing of the obtained recombinant protein on biological assays, including cell proliferation and cytokine mRNA detection by reverse transcriptase-qPCR. The results showed that out of ~50,000 genes, the hypothetical transmembrane protein-66 gene (TMEM66) exhibited a 3 times higher expression in MS patients compared to healthy subjects. The TMEM66 gene was cloned and its protein showed marked immunological activity relevant to MS since significant proliferation (P<0.05) and augmented induction of the proinflammatory cytokines, interleukin (IL)-6, interferon-γ, tumor necrosis factor-α, and the chemokines, chemokine ligand 5/chemokine receptor 5, macrophage inflammatory protein 1α (MIP-1α) and MIP-1β were recorded, but not the anti-inflammatory cytokines, IL-4 or IL-2. In conclusion, TMEM66 may be associated with the molecular events of MS and may be considered as an MS biomarker for future personalized medicine management approaches.