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cancer and inflammasome

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https://www.readbyqxmd.com/read/28634425/a-transcriptional-regulatory-role-for-the-membrane-type-1-matrix-metalloproteinase-in-carcinogen-induced-inflammasome-gene-expression
#1
Samuel Sheehy, Borhane Annabi
Signal-transducing functions driven by the cytoplasmic domain of membrane type-1 matrix metalloproteinase (MT1-MMP) are believed to regulate many inflammation-associated cancer cell functions including migration, proliferation, and survival. Aside from upregulation of the inflammation biomarker cyclooxygenase-2 (COX-2) expression, MT1-MMP's role in relaying intracellular signals triggered by extracellular pro-inflammatory cues remains poorly understood. Here, we triggered inflammation in HT1080 fibrosarcoma cells with phorbol-12-myristate-13-acetate (PMA), an inducer of COX-2 and of MT1-MMP...
2017: Gene Regulation and Systems Biology
https://www.readbyqxmd.com/read/28596252/success-in-bone-marrow-failure-novel-therapeutic-directions-based-on-the-immune-environment-of-myelodysplastic-syndromes
#2
REVIEW
Alyssa H Cull, Michael J Rauh
Myelodysplastic syndromes (MDS) are clonal neoplasms of aging that are associated with BM failure, related cytopenias, fatigue, susceptibility to infections, bruising, bleeding, a shortened lifespan, and a propensity for leukemic transformation. Most frail, elderly patients are not candidates for curative allogeneic BM transplantations and instead receive expectant management, supportive blood transfusions, or empirical, nontargeted therapy. It has been known for some time that MDS arises in an abnormal BM immune environment; however, connections have only recently been established with recurring MDS-associated mutations...
June 8, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28588495/a-brief-history-of-il-1-and-il-1-ra-in-rheumatology
#3
Jean-Michel Dayer, Francesca Oliviero, Leonardo Punzi
The history of what, in 1979, was called interleukin-1 (IL-1), orchestrator of leukocyte inter-communication, began many years before then, initially by the observation of fever induction via the endogenous pyrogen (EP) (1974) and then in rheumatology on the role in tissue destruction in rheumatoid diseases via the induction of collagenase and PGE2 in human synovial cells by a mononuclear cell factor (MCF) (1977). Since then, the family has exploded to presently 11 members as well as many membrane-bound and soluble receptor forms...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28586167/card9-dependent-il-1%C3%AE-regulates-il-22-production-from-group-3-innate-lymphoid-cells-and-promotes-colitis-associated-cancer
#4
Hanna Bergmann, Susanne Roth, Konstanze Pechloff, Elina A Kiss, Sabine Kuhn, Mathias Heikenwälder, Andreas Diefenbach, Florian R Greten, Jürgen Ruland
Inflammatory bowel diseases (IBD) are key risk factors for the development of colorectal cancer, but the mechanisms that link intestinal inflammation with carcinogenesis are insufficiently understood. Card9 is a myeloid cell-specific signaling protein that regulates inflammatory responses downstream of various pattern recognition receptors and which cooperates with the inflammasomes for IL-1β production. Because polymorphisms in Card9 were recurrently associated with human IBD, we investigated the function of Card9 in a colitis-associated cancer (CAC) model...
June 6, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28579804/expression-of-urinary-mirnas-targeting-nlrs-inflammasomes-in-bladder-cancer
#5
Ettore Mearini, Giulia Poli, Giovanni Cochetti, Andrea Boni, Maria Giulia Egidi, Stefano Brancorsini
AIM OF THE STUDY: Inflammasome, a large complex of NOD-like receptors (NLRs), drives tumor growth and progression. The present study aimed at exploring the alteration in expression of urinary inflammasome-related microRNAs (miRNAs) in bladder cancer (BC). Our previous report demonstrated the up-regulation of NLRs genes (NLRP3, NLRP4, NLRP9 and NAIP) in urine sediments of patients harboring BC. The expression levels of miRNAs targeting these NLRs (miR-146a-5p, miR-106a-5p, miR-17-5p, miR-223-3p, miR-141-3p, miR-19a-3p, miR-145-5p, miR-185-5p) were assayed in the same patient cohort...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28531279/mechanisms-governing-inflammasome-activation-assembly-and-pyroptosis-induction
#6
Sannula Kesavardhana, Thirumala-Devi Kanneganti
Inflammasomes are multimeric protein complexes that regulate inflammatory responses and pyroptotic cell death to exert host defense against microbes. Intracellular pattern-recognition receptors such as nucleotide-binding domain and leucine-rich repeat receptors (NLRs) and absent in melanoma 2 like receptors (ALRs) assemble the inflammasome complexes in response to pathogens and danger or altered-self signals in the cell. Inflammasome sensors, in association with an adaptor protein - apoptosis associated speck-like protein containing a caspase-activation and -recruitment domain (ASC) - activate inflammatory caspase-1 to enable the release of inflammatory cytokines and induce cell death, conferring host defense against pathogens...
May 20, 2017: International Immunology
https://www.readbyqxmd.com/read/28526809/tumor-cell-specific-aim2-regulates-growth-and-invasion-of-cutaneous-squamous-cell-carcinoma
#7
Mehdi Farshchian, Liisa Nissinen, Elina Siljamäki, Pilvi Riihilä, Minna Piipponen, Atte Kivisaari, Markku Kallajoki, Reidar Grénman, Juha Peltonen, Sirkku Peltonen, Koen D Quint, Jan Nico Bouwes Bavinck, Veli-Matti Kähäri
Cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer. Inflammation is a typical feature in cSCC progression. Analysis of the expression of inflammasome components in cSCC cell lines and normal human epidermal keratinocytes revealed upregulation of the expression of AIM2 mRNA and protein in cSCC cells. Elevated levels of AIM2 mRNA were noted in cSCCs in vivo compared with normal skin. Strong and moderate tumor cell specific expression of AIM2 was detected with immunohistochemistry (IHC) in sporadic human cSCCs in vivo, whereas expression of AIM2 was moderate in cSCC in situ (cSCCIS) and low or absent in actinic keratosis (AK) and normal skin...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28472897/the-anticancer-effect-of-mebendazole-may-be-due-to-m1-monocyte-macrophage-activation-via-erk1-2-and-tlr8-dependent-inflammasome-activation
#8
Kristin Blom, Wojciech Senkowski, Malin Jarvius, Malin Berglund, Jenny Rubin, Lena Lenhammar, Vendela Parrow, Claes Andersson, Angelica Loskog, Mårten Fryknäs, Peter Nygren, Rolf Larsson
Mebendazole (MBZ), a drug commonly used for helminitic infections, has recently gained substantial attention as a repositioning candidate for cancer treatment. However, the mechanism of action behind its anticancer activity remains unclear. To address this problem, we took advantage of the curated MBZ-induced gene expression signatures in the LINCS Connectivity Map (CMap) database. The analysis revealed strong negative correlation with MEK/ERK1/2 inhibitors. Moreover, several of the most upregulated genes in response to MBZ exposure were related to monocyte/macrophage activation...
May 4, 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/28459430/chemotherapy-drugs-induce-pyroptosis-through-caspase-3-cleavage-of-a-gasdermin
#9
Yupeng Wang, Wenqing Gao, Xuyan Shi, Jingjin Ding, Wang Liu, Huabin He, Kun Wang, Feng Shao
Pyroptosis, activated by the canonical caspase-1 inflammasomes or caspase-4/5/11 by cytosolic LPS, is critical for immunity(1,2,3). The caspases cleave Gasdermin D (GSDMD) in the middle linker to release autoinhibition on its Gasdermin-N domain that executes pyroptosis via the pore-forming activity(4,5,6,7,8,9). GSDMD belongs to a Gasdermin family sharing the pore-forming domain(4,6,10). The function and mechanism of activation for other Gasdermins are unknown. Here we show that GSDME, originally identified as DFNA5 (Deafness, Autosomal Dominant 5)(11), could switch TNFα or chemotherapy drugs-induced and caspase-3-mediated apoptosis to pyroptosis...
May 1, 2017: Nature
https://www.readbyqxmd.com/read/28430665/p2x7-receptor-and-nlrp3-inflammasome-activation-in-head-and-neck-cancer
#10
Ju Young Bae, Sang-Woo Lee, Yong-Hwan Shin, Jong-Ho Lee, Jeong Won Jahng, Kyungpyo Park
In this study, we investigated purinergic receptor P2X7 and NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome expressions, and their role in head and neck cancer. We found upregulation of purinergic receptor P2X7 and all NLRP3 inflammasome components in biopsied head and neck squamous cell carcinoma tissues. Similarly, the expression of purinergic receptor P2X7, apoptosis-associated speck-like protein containing CARD, and pro-form caspase 1 in A253 cells derived from epidermoid carcinoma were highly upregulated in comparison to normal Human Salivary Gland cell line...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418387/mitochondria-are-the-powerhouses-of-immunity
#11
REVIEW
Evanna L Mills, Beth Kelly, Luke A J O'Neill
Recent evidence indicates that mitochondria lie at the heart of immunity. Mitochondrial DNA acts as a danger-associated molecular pattern (DAMP), and the mitochondrial outer membrane is a platform for signaling molecules such as MAVS in RIG-I signaling, and for the NLRP3 inflammasome. Mitochondrial biogenesis, fusion and fission have roles in aspects of immune-cell activation. Most important, Krebs cycle intermediates such as succinate, fumarate and citrate engage in processes related to immunity and inflammation, in both innate and adaptive immune cells...
April 18, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28403142/melatonin-protects-rats-from-radiotherapy-induced-small-intestine-toxicity
#12
Beatriz Fernández-Gil, Ahmed E Abdel Moneim, Francisco Ortiz, Ying-Qiang Shen, Viviana Soto-Mercado, Miguel Mendivil-Perez, Ana Guerra-Librero, Darío Acuña-Castroviejo, María M Molina-Navarro, José M García-Verdugo, Ramy K A Sayed, Javier Florido, Juan D Luna, Luis Carlos López, Germaine Escames
Radiotherapy-induced gut toxicity is among the most prevalent dose-limiting toxicities following radiotherapy. Prevention of radiation enteropathy requires protection of the small intestine. However, despite the prevalence and burden of this pathology, there are currently no effective treatments for radiotherapy-induced gut toxicity, and this pathology remains unclear. The present study aimed to investigate the changes induced in the rat small intestine after external irradiation of the tongue, and to explore the potential radio-protective effects of melatonin gel...
2017: PloS One
https://www.readbyqxmd.com/read/28402258/cd200fc-reduces-lps-induced-il-1%C3%AE-activation-in-human-cervical-cancer-cells-by-modulating-tlr4-nf-%C3%AE%C2%BAb-and-nlrp3-inflammasome-pathway
#13
Aiqin He, Jia Shao, Yu Zhang, Hong Lu, Zhijun Wu, Yunzhao Xu
Chronic inflammation plays an important role in tumorigenesis of cervical cancer. CD200Fc, a CD200R1 agonist, has been found to have anti-inflammatory effects in autoimmune diseases and neuro-degeneration. However, the anti-inflammatory effect of CD200Fc on cervical cancer has not yet to be completely understood. This study investigated the anti-inflammatory effects and mechanisms of CD200Fc in LPS-induced human SiHa cells and Caski cells. SiHa cells and Caski cells were stimulated with 40 μg/ml LPS under different concentrations of CD200Fc for 90 min or 12 hours...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28380426/huaier-aqueous-extract-protects-against-dextran-sulfate-sodium-induced-experimental-colitis-in-mice-by-inhibiting-nlrp3-inflammasome-activation
#14
Lijuan Wang, Zhongxia Yu, Chao Wei, Li Zhang, Hui Song, Bing Chen, Qifeng Yang
The use of Trametes robiniophila Murr. (Huaier) as a complementary therapy for cancer has recently become increasingly common in China. However, whether Huaier can regulate host immune responses, especially innate immunity, remains largely unknown. The NLRP3 inflammasome is a multimeric complex consisting of NLRP3, ASC and caspase-1. NLRP3 inflammasomes respond to a variety of endogenous (damage-associated molecular patterns) and exogenous (pathogen-associated molecular patterns) stimuli, and play crucial roles in host defense against pathogens and multiple diseases such as ulcerative colitis (UC)...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28360909/inflammasomes-in-inflammation-induced-cancer
#15
REVIEW
Chu Lin, Jun Zhang
The inflammasome is an important multiprotein complex that functions during inflammatory immune responses. The activation of inflammasome will lead to the autoactivation of caspase-1 and subsequent cleavage of proIL-1β and proIL-18, which are key sources of inflammatory manifestations. Recently, the roles of inflammasomes in cancers have been extensively explored, especially in inflammation-induced cancers. In different and specific contexts, inflammasomes exhibit distinct and even contrasting effects in cancer development...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28279687/airborne-particulate-matter-in-vitro-exposure-induces-cytoskeleton-remodeling-through-activation-of-the-rock-mypt1-mlc-pathway-in-a549-epithelial-lung-cells
#16
Yolanda I Chirino, Claudia María García-Cuellar, Carlos García-García, Ernesto Soto-Reyes, Álvaro Román Osornio-Vargas, Luis A Herrera, Alejandro López-Saavedra, Javier Miranda, Raúl Quintana-Belmares, Irma Rosas Pérez, Yesennia Sánchez-Pérez
Airborne particulate matter with an aerodynamic diameter ≤10μm (PM10) is considered a risk factor for the development of lung cancer. Little is known about the cellular mechanisms by which PM10 is associated with cancer, but there is evidence that its exposure can lead to an acquired invasive phenotype, apoptosis evasion, inflammasome activation, and cytoskeleton remodeling in lung epithelial cells. Cytoskeleton remodeling occurs through actin stress fiber formation, which is partially regulated through ROCK kinase activation, we aimed to investigate if this protein was activated in response to PM10 exposure in A549 lung epithelial cells...
March 6, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28267621/targeting-hepatic-macrophages-to-treat-liver-diseases
#17
REVIEW
Frank Tacke
Our view on liver macrophages in the context of health and disease has been reformed by the recognition of a remarkable heterogeneity of phagocytes in the liver. Liver macrophages consist of ontogenically distinct populations termed Kupffer cells and monocyte-derived macrophages. Kupffer cells are self-renewing, resident and principally non-migratory phagocytes, serving as sentinels for liver homeostasis. Liver injury triggers Kupffer cell activation, leading to inflammatory cytokine and chemokine release. This fosters the infiltration of monocytes into the liver, which give rise to large numbers of inflammatory monocyte-derived macrophages...
March 4, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28263976/nlrp1-promotes-tumor-growth-by-enhancing-inflammasome-activation-and-suppressing-apoptosis-in-metastatic-melanoma
#18
Z Zhai, W Liu, M Kaur, Y Luo, J Domenico, J M Samson, Y G Shellman, D A Norris, C A Dinarello, R A Spritz, M Fujita
Inflammasomes are mediators of inflammation, and constitutively activated NLRP3 inflammasomes have been linked to interleukin-1β (IL-1β)-mediated tumorigenesis in human melanoma. Whereas NLRP3 regulation of caspase-1 activation requires the adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD (caspase recruitment domain)), caspase-1 activation by another danger-signaling sensor NLRP1 does not require ASC because NLRP1 contains a C-terminal CARD domain that facilitates direct caspase-1 activation via CARD-CARD interaction...
March 6, 2017: Oncogene
https://www.readbyqxmd.com/read/28260512/polypurine-reverse-hoogsteen-hairpins-as-a-gene-silencing-tool-for-cancer
#19
Carlos J Ciudad, Laura Rodríguez, Xenia Villalobos, Alex J Félix, Véronica Noé
Polypurine reverse Hoogsteen (PPRH) molecules are DNA hairpins formed by two polypurine strands running in an antiparallel orientation and containing no nucleotide modifications. The two strands, linked by a pentathymidine loop, are bound through intramolecular reverse Hoogsteen bonds. Then, PPRHs can bind by Watson-Crick bonds to their corresponding polypyrimidine target in the dsDNA provoking a displacement of the polypurine strand of the duplex. We described the effect and mechanisms of action of PPRHs in cells using PPRHs designed against the template and coding strands of the dhfr gene...
March 1, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28243117/aim2-regulates-viability-and-apoptosis-in-human-colorectal-cancer-cells-via-the-pi3k-akt-pathway
#20
Jianjun Chen, Zhenjun Wang, Sanshui Yu
Absent in melanoma 2 (AIM2) plays an important role in innate immunity as a DNA sensor in the cytoplasm by triggering the assembly of an AIM2 inflammasome that results in caspase-1-mediated inflammatory responses and cell death. In recent years, studies have indicated that AIM2 can suppress cancer cell proliferation, and mutations in the gene encoding AIM2 are frequently identified in patients with colorectal cancer (CRC). However, the mechanism by which AIM2 restricts tumor growth remains unclear. We reconstructed AIM2 expression in HCT116 CRC cells by lentivirus transfection...
2017: OncoTargets and Therapy
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