title: Modulatory effects of curcumin on apoptosis and cytotoxicity-related molecules in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients.
abstract: Apoptosis is a universal cellular defense mechanism against viral infection. Curcumin, an anti-inflammatory phytochemical, induces apoptosis through mitochondrial and receptor-mediated pathways, as well as activation of caspase cascades. Here, we investigated the impact of supplementation with curcumin on the expression of a panel of apoptosis- and cytotoxicity-related genes in patients suffering from HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP), a progressive demyelinating neuroinflammatory disease caused by HTLV-1 infection. Twenty-one HAM/TSP patients enrolled in this study. Curcumin nanomicelles (80mg/day, orally) were administered once a day for 12 weeks. The mRNA levels of total Fas (tFas), membrane-bound Fas (mFas), Fas-Ligand (FasL), TNF-related apoptosis-inducing ligand (TRAIL), perforin, granzyme A, granzyme B and granulysin were analyzed before and after treatment in peripheral blood lymphocytes. Protein levels of Fas, FasL, TRAIL and granulysin were also measured in serum using ELISA. Curcumin supplementation inhibited FasL mRNA production and up-regulated the expression of pro-apoptotic molecules granzyme A (at the mRNA level) and granulysin (at the protein level), suggesting degranulation of granulysin-bearing cells following curcumin supplementation. Conversely, Curcumin did not affect Fas, TRAIL, perforin, granzyme B at the mRNA level, and anti-apoptotic molecules sFas, sFasL and sTRAIL at the protein level. The present results suggest that curcumin supplementation increases cytotoxicity-related molecules granzyme A and granulysin in patients with HAM/TSP.
authors.affiliation: Inflammation and Inflammatory Diseases Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: Mohammadia892@mums.ac.ir.
authors.forename: Asadollah
authors.initials: A
authors.lastname: Mohammadi
authors.affiliation: Inflammation and Inflammatory Diseases Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: FazeliB@mums.ac.ir.
authors.forename: Bahare
authors.initials: B
authors.lastname: Fazeli
authors.affiliation: Department of Immunology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Electronic address: marzieh30leo@yahoo.com.
authors.forename: Marzieh
authors.initials: M
authors.lastname: Taheri
authors.affiliation: Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: sahebkara@mums.ac.ir.
authors.forename: Amirhossein
authors.initials: A
authors.lastname: Sahebkar
authors.affiliation: Inflammation and Inflammatory Diseases Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: ZohrehiPoursina@yahoo.com.
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Poursina
authors.affiliation: Community Medicine Department, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: VakiliV@mums.ac.ir.
authors.forename: Vida
authors.initials: V
authors.lastname: Vakili
authors.affiliation: Department of Neurology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: Zamanians911@mums.ac.ir.
authors.forename: Shadi Zamanian
authors.initials: SZ
authors.lastname: Yazdi
authors.affiliation: Islamic Azad University, Medical Branch of Tehran, Tehran, Iran. Electronic address: Keramati.zh@gmail.com.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Keramati
authors.affiliation: Department of Neurology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: BoostaniR@mums.ac.ir.
authors.forename: Reza
authors.initials: R
authors.lastname: Boostani
authors.affiliation: Viral Oncology Lab, University of Manchester, St Mary's Hospital, Manchester M13 9WL, UK. Electronic address: ian.hampson@manchester.ac.uk.
authors.forename: Ian
authors.initials: I
authors.lastname: Hampson
authors.affiliation: Inflammation and Inflammatory Diseases Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: RafatpanahH@mums.ac.ir.
authors.forename: Houshang
authors.initials: H
authors.lastname: Rafatpanah
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D003474:Curcumin / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D015368:Human T-lymphotropic virus 1; D006801:Humans; D008297:Male; D008875:Middle Aged; D015493:Paraparesis, Tropical Spastic / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome / Q000187:drug effects; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D003474:Curcumin
keywords: Apoptosis; Curcumin; HAM/TSP; HTLV-1; Neuroinflammatory disease