PMID- 29971065 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20181114 IS - 1664-3224 (Print) IS - 1664-3224 (Linking) VI - 9 DP - 2018 TI - Prostaglandin E2 Stimulates the Expansion of Regulatory Hematopoietic Stem and Progenitor Cells in Type 1 Diabetes. PG - 1387 LID - 10.3389/fimmu.2018.01387 [doi] AB - Hematopoietic stem and progenitor cells (HSPCs) are multipotent stem cells that have been harnessed as a curative therapy for patients with hematological malignancies. Notably, the discovery that HSPCs are endowed with immunoregulatory properties suggests that HSPC-based therapeutic approaches may be used to treat autoimmune diseases. Indeed, infusion with HSPCs has shown promising results in the treatment of type 1 diabetes (T1D) and remains the only "experimental therapy" that has achieved a satisfactory rate of remission (nearly 60%) in T1D. Patients with newly diagnosed T1D have been successfully reverted to normoglycemia by administration of autologous HSPCs in association with a non-myeloablative immunosuppressive regimen. However, this approach is hampered by a high incidence of adverse effects linked to immunosuppression. Herein, we report that while the use of autologous HSPCs is capable of improving C-peptide production in patients with T1D, ex vivo modulation of HSPCs with prostaglandins (PGs) increases their immunoregulatory properties by upregulating expression of the immune checkpoint-signaling molecule PD-L1. Surprisingly, CXCR4 was upregulated as well, which could enhance HSPC trafficking toward the inflamed pancreatic zone. When tested in murine and human in vitro autoimmune assays, PG-modulated HSPCs were shown to abrogate the autoreactive T cell response. The use of PG-modulated HSPCs may thus provide an attractive and novel treatment of autoimmune diabetes. FAU - Ben Nasr, Moufida AU - Ben Nasr M AD - Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States. AD - International Center for T1D, Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy. FAU - D'Addio, Francesca AU - D'Addio F AD - International Center for T1D, Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy. FAU - Malvandi, Amir Mohammad AU - Malvandi AM AD - International Center for T1D, Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy. FAU - Faravelli, Silvia AU - Faravelli S AD - International Center for T1D, Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy. FAU - Castillo-Leon, Eduardo AU - Castillo-Leon E AD - Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States. FAU - Usuelli, Vera AU - Usuelli V AD - Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States. AD - International Center for T1D, Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy. FAU - Rocchio, Francesca AU - Rocchio F AD - International Center for T1D, Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy. FAU - Letizia, Teresa AU - Letizia T AD - International Center for T1D, Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy. FAU - El Essawy, Abdel Basset AU - El Essawy AB AD - Medicine, Al-Azhar University, Cairo, Egypt. FAU - Assi, Emma AU - Assi E AD - International Center for T1D, Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy. FAU - Mameli, Chiara AU - Mameli C AD - Department of Pediatrics, Buzzi Children Hospital, Milan, Italy. AD - Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy. AD - Department of Pediatrics, Children's Hospital Buzzi, Milan, Italy. FAU - Giani, Elisa AU - Giani E AD - Department of Pediatrics, Buzzi Children Hospital, Milan, Italy. AD - Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy. AD - Department of Pediatrics, Children's Hospital Buzzi, Milan, Italy. FAU - Macedoni, Maddalena AU - Macedoni M AD - Department of Pediatrics, Diabetes Service Studies, University of Milan, Ospedale dei Bambini Vittore Buzzi, Milan, Italy. FAU - Maestroni, Anna AU - Maestroni A AD - International Center for T1D, Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy. FAU - Dassano, Alice AU - Dassano A AD - International Center for T1D, Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy. FAU - Loretelli, Cristian AU - Loretelli C AD - International Center for T1D, Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy. FAU - Paroni, Moira AU - Paroni M AD - Department of Bioscience, University of Milan, Milan, Italy. FAU - Cannalire, Giuseppe AU - Cannalire G AD - Department of Pediatrics and Neonatology, Ospedale Guglielmo da Saliceto, Piacenza, Italy. FAU - Biasucci, Giacomo AU - Biasucci G AD - Department of Pediatrics and Neonatology, Ospedale Guglielmo da Saliceto, Piacenza, Italy. FAU - Sala, Marco AU - Sala M AD - Department of Pediatrics, Tradate Hospital, Tradate, Italy. FAU - Biffi, Alessandra AU - Biffi A AD - Gene Therapy Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA, United States. AD - Harvard Medical School, Boston, MA, United States. FAU - Zuccotti, Gian Vincenzo AU - Zuccotti GV AD - International Center for T1D, Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy. AD - Department of Pediatrics, Buzzi Children Hospital, Milan, Italy. AD - Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy. AD - Department of Pediatrics, Children's Hospital Buzzi, Milan, Italy. FAU - Fiorina, Paolo AU - Fiorina P AD - Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States. AD - International Center for T1D, Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy. AD - Division of Endocrinology, ASST Sacco Fatebenefratelli-Sacco, Milan, Italy. LA - eng PT - Journal Article DEP - 20180619 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 PMC - PMC6018202 OTO - NOTNLM OT - CXCR4 OT - PD-L1 OT - autoimmune diseases OT - hematopoietic stem and progenitor cells OT - prostaglandins EDAT- 2018/07/05 06:00 MHDA- 2018/07/05 06:01 CRDT- 2018/07/05 06:00 PHST- 2018/03/09 00:00 [received] PHST- 2018/06/04 00:00 [accepted] PHST- 2018/07/05 06:00 [entrez] PHST- 2018/07/05 06:00 [pubmed] PHST- 2018/07/05 06:01 [medline] AID - 10.3389/fimmu.2018.01387 [doi] PST - epublish SO - Front Immunol. 2018 Jun 19;9:1387. doi: 10.3389/fimmu.2018.01387. eCollection 2018. PMID- 30336475 OWN - NLM STAT- MEDLINE DCOM- 20190128 LR - 20190128 IS - 1423-0216 (Electronic) IS - 1021-7401 (Linking) VI - 25 IP - 3 DP - 2018 TI - Human Microglial Cells Undergo Proapoptotic Induction and Inflammatory Activation upon in vitro Exposure to a Naturally Occurring Level of Aflatoxin B1. PG - 176-183 LID - 10.1159/000493528 [doi] AB - OBJECTIVE: Knowledge regarding interactions of AFB1 with the human nervous system and how a naturally occurring level of AFB1 could potentially induce neuroimmune dysregulation is very limited. To assess the cellular effects of AFB1 on the human brain, we used the human microglia cell line CHME5 as a model to pinpoint its potential in vivo translation. METHODS: We used the CHME5 cell line culture system, multiplex qPCR, (chemi)bioluminescence, Luminex ELISA, and flow cytometry assays to evaluate the toxic effects of a naturally occurring level of AFB1 on human microglia. RESULTS: A low concentration of AFB1 upregulates the mRNA expression of many proinflammatory molecules, such as TLRs, MyD88, NFkappaB, and CxCr4, induces intracellular ATP depletion, and increases caspase-3/7 activity at different time points following exposure to the toxin. Furthermore, AFB1-exposed microglia secreted significantly higher levels of IFN-gamma and GM-CSF after treatment. We also observed a slight increase in the percentage of apoptotic microglia (annexin V+/PI-) at 48 h posttreatment. CONCLUSION: Our work confirmed that the environmentally relevant level of AFB1 could cause an inflammatory reaction in human microglial cells that is potentially harmful or toxic to the homeostasis of the human central nervous system and might increase susceptibility to neurodegenerative diseases. CI - (c) 2018 S. Karger AG, Basel. FAU - Mehrzad, Jalil AU - Mehrzad J AD - Department of Microbiology and Immunology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iranmehrzad@ut.ac.ir. FAU - Hosseinkhani, Saman AU - Hosseinkhani S AD - Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran. FAU - Malvandi, Amir Mohammad AU - Malvandi AM AD - International Center for T1D, Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181018 PL - Switzerland TA - Neuroimmunomodulation JT - Neuroimmunomodulation JID - 9422763 RN - 0 (Inflammation Mediators) RN - 9N2N2Y55MH (Aflatoxin B1) SB - IM MH - Aflatoxin B1/*toxicity MH - Apoptosis/*drug effects/physiology MH - Cell Line, Transformed MH - Humans MH - Inflammation/chemically induced/metabolism MH - Inflammation Mediators/*metabolism MH - Microglia/*drug effects/*metabolism OTO - NOTNLM OT - *Aflatoxin B1 OT - *Apoptosis OT - *Human microglial cells OT - *Neurodegenerative potential OT - *Neuroinflammation EDAT- 2018/10/20 06:00 MHDA- 2019/01/29 06:00 CRDT- 2018/10/19 06:00 PHST- 2018/04/19 00:00 [received] PHST- 2018/09/05 00:00 [accepted] PHST- 2018/10/20 06:00 [pubmed] PHST- 2019/01/29 06:00 [medline] PHST- 2018/10/19 06:00 [entrez] AID - 000493528 [pii] AID - 10.1159/000493528 [doi] PST - ppublish SO - Neuroimmunomodulation. 2018;25(3):176-183. doi: 10.1159/000493528. Epub 2018 Oct 18. PMID- 28789997 OWN - NLM STAT- MEDLINE DCOM- 20170905 LR - 20170906 IS - 1879-3169 (Electronic) IS - 0378-4274 (Linking) VI - 279 DP - 2017 Sep 5 TI - Environmentally relevant level of aflatoxin B1 elicits toxic pro-inflammatory response in murine CNS-derived cells. PG - 96-106 LID - S0378-4274(17)31157-8 [pii] LID - 10.1016/j.toxlet.2017.07.902 [doi] AB - Aflatoxin B1 (AFB1) is a well-known member of aflatoxins (AFs) that is considered among highly stable toxic contaminants of food, worldwide. The impact of AFB1 on neural cells and systems has poorly been understood. To assess the cellular effects of AFB1 on brain, we used murine pure primary astrocytes, sub ventricular zone-derived neural precursor cells (NPCs) and microglia cell line (BV2). Cells were exposed separately to environmentally relevant level (20ng/ml) of AFB1 for 1, 2, 3, 6, 12, 24 and 48h in culture. At each time points, total free radicals production measured by luminol-enhanced cellular chemiluminescence (CL) assay; cytokines production of IL-1beta, IL-6, TNF-alpha and IL-10 were analyzed using Bioplex ELISA and a set of genes involved in the immediate response to danger such as TLR2, TLR4 and iNOS etc. were evaluated by multiplex qPCR. Upon AFB1 exposure production, of the total free radicals significantly increased only in microglial cells after 24h and slightly elevated in the other examined cells. AFB1 also induced secretion of pro-inflammatory cytokines (i.e. TNF-alpha and IL-6) on both microglial cells (more TNF-alpha) and astrocytes (more IL-6). mRNA expression of TLR2, TLR4, MyD88 and NF-kappaB were up-regulated with different timing and levels among cells. Immunotoxicologically, microglial cells, and astrocytes, but not NPCs, are capable of sensing a low level of AFB1. Thus, the pro-inflammatory effects of an environmentally relevant dose of AFB1 on CNS-derived cells in vitro could potentially explain the immune dysregulation in neurodegenerative disorders. CI - Copyright (c) 2017 Elsevier B.V. All rights reserved. FAU - Mehrzad, Jalil AU - Mehrzad J AD - Department of Microbiology and Immunology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran. Electronic address: mehrzad@ut.ac.ir. FAU - Malvandi, Amir Mohammad AU - Malvandi AM AD - Institute of Experimental Neurology (INSPE), San Raffaele Hospital, Via Olgettina 58, Milan, Italy. FAU - Alipour, Mohsen AU - Alipour M AD - Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran. FAU - Hosseinkhani, Saman AU - Hosseinkhani S AD - Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran. LA - eng PT - Journal Article DEP - 20170805 PL - Netherlands TA - Toxicol Lett JT - Toxicology letters JID - 7709027 RN - 0 (Free Radicals) RN - 0 (IL10 protein, mouse) RN - 0 (IL1B protein, mouse) RN - 0 (Inflammation Mediators) RN - 0 (Interleukin-1beta) RN - 0 (Interleukin-6) RN - 0 (Myd88 protein, mouse) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (NF-kappa B) RN - 0 (RNA, Messenger) RN - 0 (Tlr2 protein, mouse) RN - 0 (Tlr4 protein, mouse) RN - 0 (Toll-Like Receptor 2) RN - 0 (Toll-Like Receptor 4) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (interleukin-6, mouse) RN - 130068-27-8 (Interleukin-10) RN - 9N2N2Y55MH (Aflatoxin B1) SB - IM MH - Aflatoxin B1/*toxicity MH - Animals MH - Astrocytes/*drug effects/immunology/metabolism/pathology MH - Cell Line MH - Cell Survival/drug effects MH - Central Nervous System/*drug effects/immunology/metabolism/pathology MH - Dose-Response Relationship, Drug MH - Free Radicals/metabolism MH - Inflammation Mediators/*metabolism MH - Inhibitory Concentration 50 MH - Interleukin-10/metabolism MH - Interleukin-1beta/metabolism MH - Interleukin-6/metabolism MH - Mice MH - Microglia/*drug effects/immunology/metabolism/pathology MH - Myeloid Differentiation Factor 88/genetics/metabolism MH - NF-kappa B/genetics/metabolism MH - Neural Stem Cells/*drug effects/immunology/metabolism/pathology MH - RNA, Messenger/genetics/metabolism MH - Time Factors MH - Toll-Like Receptor 2/genetics/metabolism MH - Toll-Like Receptor 4/genetics/metabolism MH - Tumor Necrosis Factor-alpha/metabolism OTO - NOTNLM OT - Aflatoxin B(1) OT - Astrocytes OT - Microglial cells OT - Neurodegenerative diseases OT - Neuroinflammation OT - Neurotoxicity EDAT- 2017/08/10 06:00 MHDA- 2017/09/07 06:00 CRDT- 2017/08/10 06:00 PHST- 2017/02/23 00:00 [received] PHST- 2017/07/26 00:00 [revised] PHST- 2017/07/31 00:00 [accepted] PHST- 2017/08/10 06:00 [pubmed] PHST- 2017/09/07 06:00 [medline] PHST- 2017/08/10 06:00 [entrez] AID - S0378-4274(17)31157-8 [pii] AID - 10.1016/j.toxlet.2017.07.902 [doi] PST - ppublish SO - Toxicol Lett. 2017 Sep 5;279:96-106. doi: 10.1016/j.toxlet.2017.07.902. Epub 2017 Aug 5. PMID- 23786414 OWN - NLM STAT- MEDLINE DCOM- 20140204 LR - 20171116 IS - 1532-2513 (Electronic) IS - 0892-3973 (Linking) VI - 35 IP - 4 DP - 2013 Aug TI - Biologically relevant doses of mixed aflatoxins B and G up-regulate MyD88, TLR2, TLR4 and CD14 transcripts in human PBMCs. PG - 528-32 LID - 10.3109/08923973.2013.803572 [doi] AB - CONTEXT: Aflatoxins (AFs) are highly hazardous carcinogenic mycotoxins originated from very common fungi present in the environment. Their effect on key immune-surveillance molecules is unclear. OBJECTIVE: We aimed to examine the effect of mixed AFs on immunologically relevant molecules and on viability in human peripheral blood mononuclear cells (PBMCs), in conditions similar to those occurring naturally, i.e. using a mixture of environmentally relevant levels of AFB(1), AFB(2), AFG(1) and AFG(2). MATERIALS AND METHODS: We evaluated the mRNA expression of MyD88, toll-like receptor (TLR)-2, TLR4 and CD14, in human PBMCs treated with a mixture of AFB(1), AFB(2), AFG(1) and AFG(2) at different doses for 2, 12 and 24 h. We used qRT-PCR to assess changes in transcripts of MyD88, TLR2, TLR4 and CD14 in PBMCs. We also evaluated the viability of PBMCs exposed to AFs. RESULTS: Biologically relevant levels of mixed AFs elicited early immune modulation in human PBMCs. qRT-PCR results showed several folds increase of MyD88, TLR2, TLR4 and CD14 transcripts in PBMCs as early as 2 h post-exposure to mixed AFs. Kinetics and dose-response of the up-regulation differed for mentioned gene transcripts. Further, prolonged exposure to mixed AFs decreased PBMCs viability. CONCLUSION: Immunotoxicity of AFs on PBMCs may be mediated by up-regulation of key immune-surveillance molecule transcripts. The description of these effects induced by AFs on PBMCs are novel and should be taken into account when considering AF-related infectious and noninfectious diseases in areas highly exposed to AFs. FAU - Malvandi, Amir Mohammad AU - Malvandi AM AD - Department of Biochemistry, Faculty of Science, Payam Noor University of Mashhad, Iran. mehrzad@um.ac.ir FAU - Mehrzad, Jalil AU - Mehrzad J FAU - Saleh-moghaddam, Masoud AU - Saleh-moghaddam M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130621 PL - England TA - Immunopharmacol Immunotoxicol JT - Immunopharmacology and immunotoxicology JID - 8800150 RN - 0 (Lipopolysaccharide Receptors) RN - 0 (MYD88 protein, human) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (Poisons) RN - 0 (RNA, Messenger) RN - 0 (TLR2 protein, human) RN - 0 (TLR4 protein, human) RN - 0 (Toll-Like Receptor 2) RN - 0 (Toll-Like Receptor 4) RN - 9N2N2Y55MH (Aflatoxin B1) SB - IM MH - Adult MH - Aflatoxin B1/*pharmacology MH - Dose-Response Relationship, Drug MH - Humans MH - Leukocytes, Mononuclear/immunology/metabolism MH - Lipopolysaccharide Receptors/biosynthesis/*immunology MH - Male MH - Myeloid Differentiation Factor 88/biosynthesis/*immunology MH - Poisons/*pharmacology MH - RNA, Messenger/biosynthesis/immunology MH - Time Factors MH - Toll-Like Receptor 2/biosynthesis/*immunology MH - Toll-Like Receptor 4/biosynthesis/*immunology MH - Transcription, Genetic/drug effects/immunology MH - Up-Regulation/*drug effects/immunology EDAT- 2013/06/22 06:00 MHDA- 2014/02/05 06:00 CRDT- 2013/06/22 06:00 PHST- 2013/06/22 06:00 [entrez] PHST- 2013/06/22 06:00 [pubmed] PHST- 2014/02/05 06:00 [medline] AID - 10.3109/08923973.2013.803572 [doi] PST - ppublish SO - Immunopharmacol Immunotoxicol. 2013 Aug;35(4):528-32. doi: 10.3109/08923973.2013.803572. Epub 2013 Jun 21. PMID- 23492674 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20130318 LR - 20181113 IS - 2008-3866 (Print) IS - 2008-3866 (Linking) VI - 14 IP - 5 DP - 2011 Sep TI - Gene Expression Quantification of Toll like Receptors 2, 4 and Co-molecules in Human Glioblastoma Cell Line (U87-MG): Toward a New In vitro Model of Inflammation. PG - 428-35 AB - OBJECTIVES: Pattern recognition receptors (PRRs) are the main part in the innate immune response. Human glioblastoma cell line (U87-MG) is an established adherent cell line model of this common cancer; due to genetic variations between individuals it is likely more suitable for investigating molecular aspects of innate immunity. Therefore, we undertook a novel characterization of the immune phenotype of U87-MG toward establishing a base for future researches. MATERIALS AND METHODS: In this study, U87-MG cells where cultured in a normal condition, to investigate levels of toll-like receptor 2 (TLR2), TLR4, myeloid differentiation factor-88 (MyD88) and CD14 transcripts expression in these cells. Both RT-PCR and qPCR were applied to detect and quantify the expression levels of these genes in U87-MG cells and compare them to their levels in the peripheral blood mononuclear cells (PBMC) of healthy individuals, as a common reference. RESULTS: Expression level of TLR2 and TLR4 are not significantly different in U87-MG cells in comparison to PBMC. Also, expression levels of MyD88 and CD14 in U87-MG cells are significantly lower than their levels in PBMC. Furthermore, expression levels of MyD88 and CD14 in both PBMC and U87-MG are significantly lower than TLR2 and TLR4 transcripts. CONCLUSION: The data reveal expression of TLR4, CD14, MyD88 and TLR2 genes in U87-MG cell line, for the first time. Expression detection of these genes in human glioblastoma cell line might have a potential for diagnosis of inflammatory mechanisms in immune mediated disorders of in vitro models of human brain inflammatory disease. FAU - Malvandi, Amir Mohammad AU - Malvandi AM AD - Department of Biochemistry, Faculty of Science, Payam Noor University of Mashhad, Iran ; Department of Stem cells and Developmental Biology, Royan Institute for Stem cell Biology and Technology, ACECR, Tehran, Iran. FAU - Mehrzad, Jalil AU - Mehrzad J FAU - Moghaddam, Masoud Saleh AU - Moghaddam MS LA - eng PT - Journal Article PL - Iran TA - Iran J Basic Med Sci JT - Iranian journal of basic medical sciences JID - 101517966 PMC - PMC3586846 OTO - NOTNLM OT - Human glioblastoma cell line (U87-MG) OT - Innate immunity OT - Quantitative RT-PCR Toll-like receptors EDAT- 2011/09/01 00:00 MHDA- 2011/09/01 00:01 CRDT- 2013/03/16 06:00 PHST- 2010/10/23 00:00 [received] PHST- 2011/05/15 00:00 [accepted] PHST- 2013/03/16 06:00 [entrez] PHST- 2011/09/01 00:00 [pubmed] PHST- 2011/09/01 00:01 [medline] PST - ppublish SO - Iran J Basic Med Sci. 2011 Sep;14(5):428-35. PMID- 21705839 OWN - NLM STAT- MEDLINE DCOM- 20111107 LR - 20171116 IS - 1735-1383 (Print) IS - 1735-1383 (Linking) VI - 8 IP - 2 DP - 2011 Jun TI - Down-regulation of CD14 transcripts in human glioblastoma cell line U87 MG. PG - 111-9 LID - IJIv8i2A7 [doi] AB - BACKGROUND: Pattern recognition receptors (PRRs) are the main sensors of pathogen and danger signals in innate immunity of which Toll Like Receptors (TLRs) are the most studied ones. The contribution of PRRs in cerebral inflammation induced by microbial infection, tissue damage and cancer has not extensively been addressed so far. Glioma is the most common tumor of the central nervous system and glioblastomas are the most common and most malignant primary brain tumors. OBJECTIVE: The objectives of the present study were to investigate the expression of several PRRs including TLR2, TLR4, MyD88 and CD14 transcripts in human glioblastoma cell line U87 MG and compare their expression level with peripheral blood mononuclear cells (PBMC) obtained from healthy individuals. METHODS: Touchdown PCR (TD-PCR) and Real-time quantitative PCR (qPCR) were applied to detect and quantify the expression level of TLR2, TLR4, MyD88 and CD14 transcript in U87 MG cell line and (PBMC) of healthy individuals. RESULTS: According to our results, human glioblastoma cell line U87 MG expresses TLR2, TLR4, MyD88 and CD14 transcripts in TD-PCR. Moreover, the quantification of the expression of these genes revealed a highly significant down-regulation of CD14 and a slight up-regulation of TLR2 transcripts as compared to PBMC of healthy individuals. CONCLUSION: The lower expression level of CD14 in human glioblastoma cell line, might have a potential implication for CD14 mediated cerebral pathology. FAU - Haghparast, Alireza AU - Haghparast A AD - Department of Pathobiology, Ferdowsi University of Mashhad, Mashhad, Iran. alireza.haghparast@gmail.com FAU - Heidari Kharaji, Maryam AU - Heidari Kharaji M FAU - Malvandi, Amir Mohammad AU - Malvandi AM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Iran TA - Iran J Immunol JT - Iranian journal of immunology : IJI JID - 101282932 RN - 0 (Lipopolysaccharide Receptors) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (TLR2 protein, human) RN - 0 (TLR4 protein, human) RN - 0 (Toll-Like Receptor 2) RN - 0 (Toll-Like Receptor 4) SB - IM MH - Cell Line, Tumor MH - Down-Regulation/immunology MH - Gene Expression Regulation, Neoplastic MH - Glioblastoma/genetics/*immunology/*metabolism/pathology MH - Humans MH - Immunity, Innate/genetics MH - Lipopolysaccharide Receptors/genetics/immunology/*metabolism MH - Myeloid Differentiation Factor 88/genetics/metabolism MH - Polymerase Chain Reaction MH - Toll-Like Receptor 2/genetics/metabolism MH - Toll-Like Receptor 4/genetics/metabolism EDAT- 2011/06/28 06:00 MHDA- 2011/11/08 06:00 CRDT- 2011/06/28 06:00 PHST- 2011/06/28 06:00 [entrez] PHST- 2011/06/28 06:00 [pubmed] PHST- 2011/11/08 06:00 [medline] AID - 07 [pii] AID - IJIv8i2A7 [doi] PST - ppublish SO - Iran J Immunol. 2011 Jun;8(2):111-9. doi: IJIv8i2A7. PMID- 20392198 OWN - NLM STAT- MEDLINE DCOM- 20100709 LR - 20131121 IS - 1607-8888 (Electronic) IS - 1025-3890 (Linking) VI - 13 IP - 3 DP - 2010 May TI - Acute restraint stress increases the frequency of vinblastine-induced micronuclei in mouse bone marrow cells. PG - 276-80 LID - 10.3109/10253890903296710 [doi] AB - Acute physiological stress induces remarkable effects on the nervous, endocrine, and immune systems and also on cellular metabolism and cell division processes. Stress-induced instability of cellular mechanisms might play an important role in increasing cell division disorders. In this study, a relationship between stress and micronucleus (MN) induction in mouse (balb/c) bone marrow cells following vinblastine treatment, or stress or stress and vinblastine treatment in comparison to a non-stressed control group was investigated. In order to test the effects of treatments on MN induction, an in vivo MN assay was performed on bone marrow cells. The results revealed a significantly greater increase in MNs in bone marrow cells (polychromatic erythrocytes) from the stressed/vinblastine treated mice. The data indicate the ability of exposure to an emotional stressor to enhance the damaging actions on bone marrow cells of an aneugenic agent. FAU - Malvandi, Amir Mohammad AU - Malvandi AM AD - Department of Biology, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad, Iran. FAU - Haddad, Farhang AU - Haddad F FAU - Moghimi, Ali AU - Moghimi A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Stress JT - Stress (Amsterdam, Netherlands) JID - 9617529 RN - 0 (Tubulin Modulators) RN - 5V9KLZ54CY (Vinblastine) SB - IM MH - Acute Disease MH - Animals MH - Bone Marrow Cells/*drug effects/pathology MH - Dose-Response Relationship, Drug MH - Emotions MH - Erythrocytes/drug effects/physiology MH - Interphase/drug effects/physiology MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Micronuclei, Chromosome-Defective/*chemically induced MH - Mitosis/drug effects/physiology MH - Restraint, Physical MH - Stress, Psychological/*physiopathology MH - Tubulin Modulators/*toxicity MH - Vinblastine/*toxicity EDAT- 2010/04/16 06:00 MHDA- 2010/07/10 06:00 CRDT- 2010/04/16 06:00 PHST- 2010/04/16 06:00 [entrez] PHST- 2010/04/16 06:00 [pubmed] PHST- 2010/07/10 06:00 [medline] AID - 10.3109/10253890903296710 [doi] PST - ppublish SO - Stress. 2010 May;13(3):276-80. doi: 10.3109/10253890903296710.