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toll like receptors and lymphoma

A M El Tawdy, I M Amin, R M Abdel Hay, A S Hassan, Z S Gad, L A Rashed
BACKGROUND: Toll-like receptors (TLRs) have been implicated in various dermatological diseases. TLR agonists have the capacity to potently activate the innate immune cells of patients with advanced, refractory, cutaneous T-cell lymphoma (CTCL). AIM: To detect TLR7 gene expression in mycosis fungoides (MF) (a neoplastic skin condition) and to compare it with psoriasis (an inflammatory skin condition) in an attempt to clarify the pathogenic role played by TLR7 in both conditions...
January 5, 2017: Clinical and Experimental Dermatology
Joel R Wilmore, Alexander C Maue, Rosemary Rochford
INTRODUCTION: Endemic Burkitt's lymphoma (eBL) is associated with Epstein-Barr virus and repeated malaria infections. A defining feature of eBL is the translocation of the c-myc oncogene to the control of the immunoglobulin promoter. Activation-induced cytidine deaminase (AID) has been shown to be critical for this translocation. Malaria infection induces AID in germinal center B cells, but whether malaria infection more broadly affects AID activation in extrafollicular B cells is unknown...
December 2016: Immunity, Inflammation and Disease
Sreya Bagchi, Sha Li, Chyung-Ru Wang
Adoptive immunotherapy for cancer treatment is an emerging field of study. Till now, several tumor-derived, peptide-specific T cell responses have been harnessed for treating cancers. However, the contribution of lipid-specific T cells in tumor immunity has been understudied. CD1 molecules, which present self- and foreign lipid antigens to T cells, are divided into group 1 (CD1a, CD1b, and CD1c) and group 2 (CD1d). Although the role of CD1d-restricted natural killer T cells (NKT) in several tumor models has been well established, the contribution of group 1 CD1-restricted T cells in tumor immunity remains obscure due to the lack of group 1 CD1 expression in mice...
2016: Oncoimmunology
Maren Feist, Judith Kemper, Franziska Taruttis, Thorsten Rehberg, Julia C Engelmann, Wolfram Gronwald, Michael Hummel, Rainer Spang, Dieter Kube
A network of autocrine and paracrine signals defines B cell homeostasis and is thought to be involved in transformation processes. Investigating interactions of these microenvironmental factors and their relation to proto-oncogenes as c-Myc (MYC) is fundamental to understand the biology of B cell lymphoma. Therefore, B cells with conditional MYC expression were stimulated with CD40L, insulin-like growth factor 1, α-IgM, Interleukin-10 (IL10) and CpG alone or in combination. The impact of forty different interventions on cell proliferation was investigated in MYC deprived cells and calculated by linear regression...
September 26, 2016: International Journal of Cancer. Journal International du Cancer
Gabriela Maria Wiedemann, Severin Johannes Jacobi, Michael Chaloupka, Angelina Krächan, Svetlana Hamm, Stefan Strobl, Roland Baumgartner, Simon Rothenfusser, Peter Duewell, Stefan Endres, Sebastian Kobold
Toll-like receptor 7 (TLR7) agonists are potent immune stimulants able to overcome cancer-associated immune suppression. Due to dose-limiting systemic toxicities, only the topically applied TLR7 agonist (imiquimod) has been approved for therapy of skin tumors. There is a need for TLR7-activating compounds with equivalent efficacy but less toxicity. SC1, a novel small molecule agonist for TLR7, is a potent type-1 interferon inducer, comparable to the reference TLR7 agonist resiquimod, yet with lower induction of proinflammatory cytokines...
July 2016: Oncoimmunology
Maria Batool, Muhammad Ayaz Anwar, Sangdun Choi
The crucial role of Toll-like Receptors (TLRs) in innate and adaptive immune systems is well discussed in the literature. In cancer, TLRs act as a double-edged sword that can promote or suppress tumor growth. Areas covered: In this article, the authors uncover the potential role of TLRs in lymphomas, which are cancers related to the lymphatic system and blood cells. TLRs are de facto inflammation-inducing receptors that can either worsen disease or ameliorate lymphoma treatment. From this perspective, the usage of TLRs to modulate the immune system toward lymphoma regression is desirable...
November 2016: Expert Opinion on Drug Discovery
Chendi Zhan, Ruxi Qi, Guanghong Wei, Emine Guven-Maiorov, Ruth Nussinov, Buyong Ma
MyD88 is an essential adaptor protein, which mediates the signaling of the toll-like and interleukin-1 receptors' superfamily. The MyD88 L252P (L265P) mutation has been identified in diffuse large B-cell lymphoma. The identification of this mutation has been a major advance in the diagnosis of patients with aldenstrom macroglobulinemia and related lymphoid neoplasms. Here we used computational methods to characterize the conformational effects of the mutation. Our molecular dynamics simulations revealed that the mutation allosterically quenched the global conformational dynamics of the toll/IL-1R (TIR) domain, and readjusted its salt bridges and dynamic community network...
September 2016: Protein Engineering, Design & Selection: PEDS
Xibao Zhao, Huihui Zhu, Juan Yu, Hongrui Li, Jiafeng Ge, Weilin Chen
Induction of type I interferon is a fundamental cellular response to viral infection. Interferon regulatory factor 3 (IRF3) plays an essential role in Toll-like receptor (TLR) and retinoic acid-inducible gene I (RIG-I) mediated induction of type I interferon and host antiviral responses. However, posttranslational regulation of IRF3 remains to be fully understood. In this study, we identified E3 ubiquitin ligase Casitas B-lineage lymphoma (c-Cbl) as a negative regulator for IRF3 protein stability and IFN-β signal pathway...
November 2016: Cellular Signalling
Larry Mansouri, Nikos Papakonstantinou, Stavroula Ntoufa, Kostas Stamatopoulos, Richard Rosenquist
The nuclear factor-κB (NF-κB) pathway is constitutively activated in chronic lymphocytic leukemia (CLL) patients, and hence plays a major role in disease development and evolution. In contrast to many other mature B-cell lymphomas, only a few recurrently mutated genes involved in canonical or non-canonical NF-κB activation have been identified in CLL (i.e. BIRC3, MYD88 and NFKBIE mutations) and often at a low frequency. On the other hand, CLL B cells seem 'addicted' to the tumor microenvironment for their survival and proliferation, which is primarily mediated by interaction through a number of cell surface receptors, e...
August 2016: Seminars in Cancer Biology
Ji-Young Choe, Mira Park, Ji Yun Yun, Hee Young Na, Heounjeong Go, Hyun-Jung Kim, Sohee Oh, Ji Eun Kim
PELI is a family of E3 ubiquitin ligases that regulate protein activity through a post-translational modification, ubiquitination. While PELI1 has been found to play a pivotal role in inflammatory processes through the activation of Toll-like receptor signaling and the NF-kB pathway, the role of PELI1 in oncogenesis has not been the subject of much investigation. We aimed to explore PELI1 expression in various malignant lymphomas and identify clinicopathologic significance. Immunohistochemistry for PELI1 was performed on a total of 502 cases, including 406 B-cell, 76 T or NK-cell, and 20 Hodgkin lymphomas...
November 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
James Q Wang, Bruce Beutler, Christopher C Goodnow, Keisuke Horikawa
The MYD88(L265P) mutation is found in 2% to 10% of chronic lymphocytic leukemia, 29% of activated B-cell type diffuse large B-cell lymphoma and 90% of Waldenström macroglobulinemia, making it conceptually attractive to treat these malignancies with inhibitors of endosomal Toll-like receptors (TLR9, TLR7) that activate MYD88. Here we show that genetic inhibition of endosomal TLRs has the opposite effect on accumulation of MYD88(L265P) B cells in vitro and in vivo. Activated mature B cells from wild-type, Unc93b1(3d/3d)-mutant, or Tlr9-deficient mice were transduced with retrovirus encoding MYD88(L265P) and analyzed either in vitro or after transplantation into Rag1(-/-) recipient mice...
September 22, 2016: Blood
Stavroula Ntoufa, Maria Giovanna Vilia, Kostas Stamatopoulos, Paolo Ghia, Marta Muzio
Malignancies of mature B cells are quite distinctive in originating from well-differentiated cells. Hence, it is not paradoxical that, similar to their normal counterparts, most mature B cell lymphoma subtypes are critically dependent on microenvironmental cues. Such external signals are sensed by various receptors present on the malignant cells, including the Toll-like receptors (TLRs), eliciting a range of cellular responses, including proliferation but also anergy and apoptosis, often with disease-specific patterns...
August 2016: Seminars in Cancer Biology
Yoon Hee Chung, Daejin Kim
BACKGROUND: Phosphorylation of glycogen synthase kinase 3β (GSK3β) by phosphatidyl-inositide 3-kinase (PI3K)/protein kinase B (AKT) or inhibition of GSK3β with small-molecule inhibitor attenuates cell survival and proliferation and increases apoptosis in most cancer cell lines. In this study, we investigated the role of phosphorylated GSK3β activated by enhanced toll-like receptor 4 (TLR4) expression in drug-treated colon cancer cells as a model of post-chemotherapy cancer cells. MATERIALS AND METHODS: The effect of TLR4 stimulation on metastasis and apoptosis in drug-exposed colon cancer cells was determined by real-time polymerase chain reaction (PCR) and immunoblotting...
July 2016: Anticancer Research
H M Lee, H J Jang, S S Kim, H J Kim, S Y Lee, M Y Oh, H C Kwan, D S Jang, D W Eom
BACKGROUND: Eupatilin, a pharmacologically active flavone derived from Artemisia species, is known to have antioxidant and antiinflammatory activities. Ischemia-reperfusion injury (IRI) is a major critical event that commonly occurs after liver transplantation and resection. Furthermore, inflammatory responses to IRI exacerbate the resultant hepatic injury. In this study, we investigated whether eupatilin protects against IR-induced acute liver injury in mice. MATERIALS AND METHODS: Partial (70%) hepatic IRI was induced in male C57BL/6 mice by portal triad pedicle occlusion for 90 minutes followed by reperfusion for 6 hours...
May 2016: Transplantation Proceedings
Michiel van den Brand, Jos Rijntjes, Konnie M Hebeda, Laura Menting, Carolyn V Bregitha, Wendy B C Stevens, Walter J F M van der Velden, Bastiaan B J Tops, J Han J M van Krieken, Patricia J T A Groenen
AIMS: To investigate the spectrum of mutations in 20 genes involved in B-cell receptor and/or Toll-like receptor signalling resulting in activation of nuclear factor-κB (NF-κB) in 20 nodal marginal zone lymphomas (NMZLs), 20 follicular lymphomas (FLs), and 11 cases of B-cell lymphoma, unclassifiable (BCL-u). METHODS AND RESULTS: Nodal marginal zone lymphomas were diagnosed according to strict criteria, including the expression of at least one putative marginal zone marker (MNDA and/or IRTA1)...
January 2017: Histopathology
Paloma Martin, Jimena Martínez-Velasquez, Maria Jose Coronado, Isabel Krsnik, Mariano Provencio, Belen Navarro, Manuela Moraru, Carmen Bellas, Carlos Vilches, Natalia Gomez-Lozano
Classical Hodgkin lymphoma (cHL) is frequently related to Epstein-Barr virus (EBV) infection. Its malignant capacity is attributed to disruption of an EBV-host balance influenced by environmental and genetic drivers. EBV structures activate Type I interferon (IFN) pathway of the innate immunity, therefore, genetic polymorphisms could influence this response. We explored the impact of four single nucleotide polymorphisms (SNPs) on EBV-associated cHL susceptibility. Toll-like receptors 9 (TLR9_rs5743836), and 3 (TLR3_rs3775291), Interleukin-28B (IL28B_rs12979860), and DEAD-box polypeptide 58 (DDX58_rs10813831) were genotyped in 73 EBV-positive and 106 EBV-negative cHL patients and 396 controls...
June 7, 2016: Leukemia & Lymphoma
Xiang Hu, Chaofeng Han, Jing Jin, Kewei Qin, Hua Zhang, Tianliang Li, Nan Li, Xuetao Cao
Interleukin-10 (IL-10) plays a central role in regulation of intestinal mucosal homeostasis and prevention of inflammatory bowel disease (IBD). We previously reported that CD11b(hi) regulatory dendritic cells (DCs) can produce more IL-10, and CD11b can negatively regulate Toll-like receptors (TLRs)-induced inflammatory responses in macrophages. However whether CD11b and its signaling can control autoimmunity via IL-10 production remains unclear. Here we found that CD11b deficient (Itgam(-/-)) mice were more susceptible to dextran sulfate sodium (DSS)-induced colitis, with more tumor necrosis factor α (TNF-α) while less IL-10 production...
2016: Scientific Reports
Valli De Re, Mariangela De Zorzi, Laura Caggiari, Gianfranco Lauletta, Maria Lina Tornesello, Elisa Fognani, Marta Miorin, Vito Racanelli, Luca Quartuccio, Laura Gragnani, Sabino Russi, Fabio Pavone, Michela Ghersetti, Elena Garlatti Costa, Pietro Casarin, Riccardo Bomben, Cesare Mazzaro, Giancarlo Basaglia, Massimiliano Berretta, Emanuela Vaccher, Francesco Izzo, Franco Maria Buonaguro, Salvatore De Vita, Anna Linda Zignego, Paolo De Paoli, Riccardo Dolcetti
To explore the relationship between innate immunity and hepatitis C Virus (HCV) in determining the risk of cirrhosis (CIR), hepatocellular carcinoma (HCC), mixed cryoglobulinemia syndrome (MCS) and non-Hodgkin lymphoma (NHL), we investigated the impact of the toll-like receptor-2 (TLR2) and interleukin-28B (IL28B) genetic variants. TLR2 -174 del variant was associated with TLR2 expression and with specific downstream molecules that drive the expression of different interleukins; rs12979860 Il28B was important in response to interferon-treatment and in spontaneous clearance of HCV...
June 21, 2016: Oncotarget
Nadine Voelxen, Claudia Wehr, Sylvia Gutenberger, Baerbel Keller, Miriam Erlacher, Cecilia Dominguez-Conde, Daniela Bertele, Florian Emmerich, Milena Pantic, Stefanie Jennings, Mirzokhid Rakhmanov, Christian Foerster, Uwe M Martens, Uwe Platzbecker, Hans-Hartmut Peter, Paul Fisch, Kaan Boztug, Hermann Eibel, Ulrich Salzer, Klaus Warnatz
Persistent polyclonal B lymphocytosis (PPBL) is a benign hematological disorder characterized by a selective expansion of circulating polyclonal marginal zone-like B cells. Previous reports demonstrated that cases of PPBL showed poor activation, proliferation, and survival of B cells in vitro, yet the underlying defect remains unknown. Here, we report for the first time an attenuated activation of the canonical NF-κB and MAPK/ERK pathway after CD40 stimulation. This defect was selective, as alternative NF-κB signaling after CD40 stimulation and both B cell receptor (BCR) and toll-like receptor 9 (TLR9) mediated activation remained unaffected...
April 29, 2016: Immunology and Cell Biology
Katy Mastorci, Elena Muraro, Elisa Pasini, Chiara Furlan, Luca Sigalotti, Marina Cinco, Riccardo Dolcetti, Elisabetta Fratta
Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin's lymphoma with a still undefined etiology. Several lines of evidence are consistent with the possible involvement of peculiar microenvironmental stimuli sustaining tumor cell growth and survival, as the activation of Toll-like receptors (TLR) 4 and 9. However, little is known about the contribution of other TLRs of pathogenic relevance in the development of MCL. This study reports evidence that MCL cell lines and primary MCL cells express different levels of TLR2 and TLR5, and that their triggering is able to further activate the Akt, MAPK, and NF-κB signaling cascades, known to be altered in MCL cells...
2016: PloS One
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