The Experts below are selected from a list of 300 Experts worldwide ranked by ideXlab platform
Jin Sup Jung - One of the best experts on this subject based on the ideXlab platform.
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Role of toll-like receptors on human adipose-derived stromal cells.
Stem cells (Dayton Ohio), 2006Co-Authors: Hyun Hwa Cho, Yong Chan Bae, Jin Sup JungAbstract:Adult mesenchymal stem cells (MSCs) are promising tools for such applications as tissue engineering and cellular therapy. It is not clear how stem cells exposed to unfavorable conditions (e.g., hypoxia or inflammation) respond to signals of danger after in vivo transplantation. Toll-like receptors (TLRs) play a major role in the immune system, participating in the initial recognition of microbial pathogens and pathogen-associated components. This study was designated to determine the role of TLRs in human MSCs. Reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometry analysis demonstrated that MSCs derived from human adipose tissue and bone marrow express TLR-1, TLR-2, TLR-3, TLR-4, TLR-5, TLR-6, and TLR-9. We investigated induction of the differentiation and proliferation of human adipose tissue stromal cells (hADSCs) by TLR agonists, including flagellin, peptidoglycans (PGN), lipopolysaccharide (LPS), the synthetic double-stranded RNA analog poly(I:C), and synthetic CpG oligodeoxydinucleotide (CpG-ODN). None of these agonists, except ODN, affected the proliferation of hADSCs. LPS and PGN increased osteogenic differentiation, but CpG-ODN decreased it. Poly(I:C) itself did not affect adipogenic or osteogenic differentiations, but exerted a synergistic effect on LPS- or PGN-induced osteogenic differentiation. RT-PCR analysis demonstrated that LPS and PGN induce osteogenic markers in hADSCs. TLR agonists affected the expression of chemokines and cytokines differentially. Furthermore, hADSCs affected the expression of specific TLRs in vitro under hypoxic conditions. These data provide evidence of a nonimmune role for TLR signaling on MSCs and may provide clues to the behavior of transplanted MSCs in vivo.
Frank A Redegeld - One of the best experts on this subject based on the ideXlab platform.
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toll like receptor TLR 1 2 triggering of multiple myeloma cells modulates their adhesion to bone marrow stromal cells and enhances bortezomib induced apoptosis
PLOS ONE, 2014Co-Authors: Jahangir Abdi, Tuna Mutis, Johan Garssen, Frank A RedegeldAbstract:In multiple myeloma (MM), the malignant plasma cells usually localize to the bone marrow where they develop drug resistance due to adhesion to stromal cells and various environmental signals. Hence, modulation of this interaction is expected to influence drug sensitivity of MM cells. Toll-like receptor (TLR) ligands have displayed heterogeneous effects on B-cell malignancies and also on MM cells in a few recent studies, but effects on adhesion and drug sensitivity of myeloma cells in the context of bone marrow stromal cells (BMSCs) have never been investigated. In the present study, we explored the modulatory effects of TLR1/2 ligand (Pam3CSK4) on adhesion of human myeloma cells to BMSCs. It is shown that TLR1/2 triggering has opposite effects in different HMCLs on their adhesion to BMSCs. Fravel, L363, UM-6, UM-9 and U266 showed increased adhesion to BMSC in parallel with an increased surface expression of integrin molecules α4 and αVβ3. OPM-1, OPM-2 and NCI-H929 showed a dose-dependent decrease in adhesion upon TLR activation following a downregulation of β7 integrin expression. Importantly, TLR1/2 triggering increased cytotoxic and apoptotic effects of bortezomib in myeloma cells independent of the effect on stromal cell adhesion. Moreover, the apoptosis-enhancing effect of Pam3CSK4 paralleled induction of cleaved caspase-3 protein in FACS analysis suggesting a caspase-dependent mechanism. Our findings uncover a novel role of TLR activation in MM cells in the context of bone marrow microenvironment. Stimulation of TLR1/2 bypasses the protective shield of BMSCs and may be an interesting strategy to enhance drug sensitivity of multiple myeloma cells.
G F Wiegertjes - One of the best experts on this subject based on the ideXlab platform.
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molecular and functional characterization of toll like receptor TLR 1 and TLR2 in common carp cyprinus carpio
Fish & Shellfish Immunology, 2016Co-Authors: Inge R Fink, D Pietretti, Carlos G P Voogdt, Adrie H Westphal, H F J Savelkoul, Maria Forlenza, G F WiegertjesAbstract:Toll-like receptors (TLRs) are fundamental components of innate immunity that play significant roles in the defence against pathogen invasion. In this study, we present the molecular characterization of the full-length coding sequence of TLR1, TLR2a and TLR2b from common carp (Cyprinus carpio). Each is encoded within a single exon and contains a conserved number of leucine-rich repeats, a transmembrane region and an intracellular TIR domain for signalling. Indeed, sequence, phylogenetic and synteny analysis of carp TLR1, TLR2a and TLR2b support that these genes are orthologues of mammalian TLR1 and TLR2. The TLR genes are expressed in various immune organs and cell types. Furthermore, the carp sequences exhibited a good three-dimensional fit with the heterodimer structure of human TLR1-TLR2, including the potential to bind to the ligand Pam3CSK4. This supports the possible formation of carp TLR1-TLR2 heterodimers. However, we were unable to demonstrate TLR1/TLR2-mediated ligand binding in transfected cell lines through NF-κB activation, despite showing the expression and co-localization of TLR1 and TLR2. We discuss possible limitations when studying ligand-specific activation of NF-κB after expression of TLR1 and/or TLR2 in human but also fish cell lines and we propose alternative future strategies for studying ligand-binding properties of fish TLRs.
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FACING THE CHALLENGE OF A FUNCTIONAL CHARACTERIZATION OF TOLL-LIKE RECEPTOR (TLR)1 AND TLR2 IN COMMON CARP
Fish & Shellfish Immunology, 2016Co-Authors: Inge R Fink, D Pietretti, Maria Forlenza, G F WiegertjesAbstract:Toll-like receptors are a family of germline-encoded pattern recognition receptors which activate rapid inflammatory responses upon detection of their cognate ligands. In mammals, TLR2 can form a heterodimer with TLR1, 6, or 10, and recognize lipoproteins/lipopeptides from Gram-positive bacteria. Of these TLRs, only TLR1 and TLR2 are present in fish genomes. In the carp genome, a single full-length TLR1 gene could be identified, whereas two functional genes for carp TLR2 exist. High expression of TLR1 and both TLR2 genes was found in immune organs and leukocytes of both myeloid and lymphoid origin. Of the two TLR2 genes, TLR2a was always higher expressed than TLR2b. Three-dimensional modelling of the carp TLR1 and TLR2 proteins appear to confirm the ability to form a heterodimer, with a pocket that can accommodate the tri-acylated lipopeptide ligand Pam3CSK4, similar to the heterodimer structure of human TLR1-TLR2 on which the model was built. In cell lines of human as well as fish origin transfected to overexpress the carp TLR proteins, co-localization of carp TLR1 and TLR2 could be revealed with confocal microscopy. We were unable to confirm TLR localization to the cell surface, the expected sub-cellular localization of TLR1 and TLR2. Further experimental evidence would be needed to unequivocally prove molecular interaction between the two TLR proteins. In previous work, we have described ligand-specific activation of carp TLR2 overexpressed in human cells (HEK), via measurement of increased phosphorylation levels of the MAP kinase p38 by Western blot. Instead of this semi-quantitative method, here we used a read-out system based on NF-κB activation and subsequent measurement of luminescence. This quantitative method could not confirm our initial ligand binding studies, not using human cell lines (HEK, HeLa), nor using a fish cell line (EPC). We will discuss possible explanations for the unsuccessful ligand-specific activation of NF-κB after overexpression of TLR1 and/or TLR2 in human, but also fish cell lines, to propose alternative future strategies for studying ligand binding properties of fish TLRs.
Ralf R. Schumann - One of the best experts on this subject based on the ideXlab platform.
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Erratum: Less functional variants of TLR-1/-6/-10 genes are associated with age
Immunity & Ageing, 2015Co-Authors: Lutz Hamann, Juozas Kupcinskas, Jurgita Skieceviciene, Andre Franke, Ute Nothlings, Luis C. Almanza Berrocal, Ralf R. SchumannAbstract:After publication of this study [1], the authors noticed that the spelling of author Luis C Berrocal Almanza’s name was incorrect. The original version of this article has been updated to correct this. The publisher apologises for any inconvenience caused.
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less functional variants of TLR 1 6 10 genes are associated with age
Immunity & Ageing, 2015Co-Authors: Lutz Hamann, Juozas Kupcinskas, Luis Berrocal C Almanza, Jurgita Skieceviciene, Andre Franke, Ute Nothlings, Ralf R. SchumannAbstract:Background Determining the prerequisites for healthy aging is a major task in the modern world characterized by a longer lifespan of the individuals. Besides lifestyle and environmental influences genetic factors are involved as shown by several genome-wide association studies. Older individuals are known to have an impaired immune response, a condition recently termed “inflamm-aging”. We hypothesize that the induction of this condition in the elderly is influenced by the sensitivity of the innate immune system. Therefore, we investigated genetic variants of the Toll-like receptor (TLR) family, one of the major family of innate immune receptors, for association with age in two cohorts of healthy, disease-free subjects.
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The toll-like receptor 1 variant S248N influences placental malaria.
Infection Genetics and Evolution, 2010Co-Authors: Lutz Hamann, George Bedu-addo, Teunis A. Eggelte, Ralf R. Schumann, Frank P. MockenhauptAbstract:Abstract In malaria-endemic regions, Plasmodium falciparum infection in pregnancy is a predominant cause of maternal and infant morbidity and mortality. Primiparae are relatively immune-naive and particularly prone. Innate immune recognition of P. falciparum is partly mediated by Toll-like receptors (TLRs), and single nucleotide polymorphisms (SNPs) of TLR-4 and -9 influence manifestation. Recognition via TLR-2, which functions as heterodimer with TLR-1 or TLR-6, appears to be essential but in previous studies from Ghana, functional TLR-2 SNPs were virtually absent. In the present study, we assessed two well characterized TLR-1 polymorphisms, rs4833095 (S248N) and rs5743618 (I602S), among 302 primiparous Ghanaian women, and analysed associations with P. falciparum infection and manifestation. The prevalence of the TLR-1 S248N variant was 20.5%, whereas the TLR-1 I602S variant was rare at 2%. Placental P. falciparum infection was observed in 78% of women heterozygous for the TLR-1 S248N SNP but in 63% of women with the respective wildtype (P = 0.03). Furthermore, the odds of malaria-associated anaemia were more than doubled in TLR-1 S248N heterozygous women (P = 0.03) although parasite densities did not differ. No differences in the rates of low birth weight and preterm delivery were observed. These data support that TLR-1 is involved in the recognition of P. falciparum and indicate its role in susceptibility to and manifestation of malaria in pregnancy.
Maria Heloisa Souza Lima Blotta - One of the best experts on this subject based on the ideXlab platform.
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TLR 2 TLR 4 and dectin 1 expression in human monocytes and neutrophils stimulated by paracoccidioides brasiliensis
Medical Mycology, 2009Co-Authors: Camila Vicente Bonfim, Ronei Luciano Mamoni, Maria Heloisa Souza Lima BlottaAbstract:AbstractParacoccidioidomycosis (PCM) is an endemic mycosis in Latin America caused by the dimorphic fungus Paracoccidioides brasiliensis. The pattern of the immune responses to P. brasiliensis determines the disease progression and clinical outcome. Innate immune response is mediated by phagocytic cells, such as macrophage and neutrophils, which ingest and kill invading pathogens and then trigger the adaptive immune system through the secretion of cytokines and chemokines. The C-type like lectin receptors (CLR) and Toll-like receptors (TLRs) are the two main pattern recognition receptors in phagocytic cells that recognize fungal components. Therefore, the purpose of the present study was to evaluate the expression of TLR-1, TLR-2, TLR-4 and dectin-1 (CLR) in monocytes and neutrophils from healthy individuals after stimulation with Pb18 (high virulence) and Pb265 (low virulence) yeasts of P. brasiliensis. As positive controls we used specific ligands to TLR-4 (LPS), TLR-2 and dectin-1 (zymosan). Our result...