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https://www.readbyqxmd.com/read/28804220/antitumor-macrophage-response-to-bacillus-pumilus-ribonuclease-binase
#1
Anna Makeeva, Julian Rodriguez-Montesinos, Pavel Zelenikhin, Alexander Nesmelov, Klaus T Preissner, Hector A Cabrera-Fuentes, Olga N Ilinskaya
Extracellular bacterial ribonucleases such as binase from Bacillus pumilus possess cytotoxic activity against tumor cells with a potential for clinical application. Moreover, they may induce activation of tumor-derived macrophages either into the M1-phenotype with well-documented functions in the regulation of the antitumor immune response or into M2-macrophages that may stimulate tumor growth, metastasis, and angiogenesis. In this study, binase or endogenous RNase1 (but not RNA or short oligonucleotides) stimulated the expression of activated NF-κB p65 subunit in macrophages...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28801798/downregulation-of-paralemmin-3-ameliorates-lipopolysaccharide-induced-acute-lung-injury-in-rats-by-regulating-inflammatory-response-and-inhibiting-formation-of-tlr4-myd88-and-tlr4-trif-complexes
#2
Xuxin Chen, Lu Tang, Jian Feng, Yi Wang, Zhihai Han, Jiguang Meng
Previous studies have demonstrated paralemmin-3 (PALM3) participates in Toll-like receptor (TLR) signaling. This study investigated the effect of PALM3 knockdown on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and its underlying mechanisms. We constructed a recombinant adenoviral vector containing short hairpin RNA for PALM3 to knockdown PALM3 expression. A transgene-free adenoviral vector was used as a negative control. The ALI rat model was established by LPS peritoneal injection at 48-h post-transfection...
August 12, 2017: Inflammation
https://www.readbyqxmd.com/read/28801624/stingray-venom-activates-il-33-producing-cardiomyocytes-but-not-mast-cell-to-promote-acute-neutrophil-mediated-injury
#3
Janaina Cardoso Dos Santos, Lidiane Zito Grund, Carla Simone Seibert, Elineide Eugênio Marques, Anderson Brito Soares, Valerie F Quesniaux, Bernhard Ryffel, Monica Lopes-Ferreira, Carla Lima
One of the hallmarks of acute inflammation is neutrophil infiltration of tissues. We investigated molecular mechanisms implicated in acute neutrophilic inflammation induced by the venom of a freshwater stingray (Potamotrygon cf. henlei) in mice. Ray venom induced early mobilization of neutrophil in the microvasculature of cremaster mice and infiltration of the peritoneal cavity 2 hours after injury, in a dose-response manner. IL-1β, IL-6, TNF-α, and KC were produced. The neutrophilic infiltration did not occur in mice with ST2 receptor and MyD88 adapters neutralized, or in those with PI3K and p38 MAPK signaling blocked...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28795664/-roles-of-myd88-and-trif-in-cardiac-dysfunction-during-sepsis
#4
Yun Zhu, Ming Zhang, Minzhi Ouyang, Dan Zhou, Ling Li
OBJECTIVE: To investigate the roles of myeloid differentiation factor 88 (MyD88) and TIR domain-containing adaptor inducing interferon-β (TRIF) in sepsis-induced myocardial dysfunction, and to analyze whether strain rate (SR) can be early sensitive evaluation for septic heart failure. METHODS: Sixty-four healthy male C57BL/6 mice were divided into four groups by random number table (n = 16 in each group): sham group, cecum ligation and puncture (CLP)-induced sepsis model group, anti-MyD88 group and anti-TRIF group...
August 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28790362/double-stranded-rna-induces-chicken-t-cell-lymphoma-apoptosis-by-trif-and-nf-%C3%AE%C2%BAb
#5
Haitao Zou, Ruixue Su, Jing Ruan, Hongxia Shao, Kun Qian, Jianqiang Ye, Yongxiu Yao, Venugopal Nair, Aijian Qin
Toll-like receptor-3 (TLR3), a member of the pathogen recognition receptor family, has been reported to activate immune response and to exhibit pro-apoptotic activity against some tumor cells. However it is unclear whether TLR3 has same function against chicken lymphoma. In this paper we investigated the effect of TLR3 activation on a Marek's disease lymphoma-derived chicken cell line, MDCC-MSB1. The TLR3 agonist poly (I:C) activated TLR3 pathway and inhibited tumor cells proliferation through caspase-dependent apoptosis...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28790196/trif-dependent-toll-like-receptor-signaling-suppresses-scd1-transcription-in-hepatocytes-and-prevents-diet-induced-hepatic-steatosis
#6
Jing Chen, Jin Li, Jensen H C Yiu, Jenny K W Lam, Chi-Ming Wong, Bernhard Dorweiler, Aimin Xu, Connie W Woo
Nonalcoholic fatty liver disease (NAFLD) includes a spectrum of diseases that ranges in severity from hepatic steatosis to steatohepatitis, the latter of which is a major predisposing factor for liver cirrhosis and cancer. Toll-like receptor (TLR) signaling, which is critical for innate immunity, is generally believed to aggravate disease progression by inducing inflammation. Unexpectedly, we found that deficiency in TIR domain-containing adaptor-inducing interferon-β (TRIF), a cytosolic adaptor that transduces some TLR signals, worsened hepatic steatosis induced by a high-fat diet (HFD) and that such exacerbation was independent of myeloid cells...
August 8, 2017: Science Signaling
https://www.readbyqxmd.com/read/28774595/interleukin-36%C3%AE-induced-by-the-tlr3-slug-vdr-axis-promotes-wound-healing-via-reg3a
#7
Ziwei Jiang, Yuanqi Liu, Changwei Li, Leilei Chang, Wang Wang, Zhenhua Wang, Xiaoguang Gao, Bernhard Ryffel, Yelin Wu, Yuping Lai
Interleukin-36 (IL-36) family members are highly expressed in hyperproliferative keratinocytes and play an important role in the pathogenesis of skin diseases such as psoriasis. However, whether and how IL-36 cytokines are induced to promote wound healing remains unknown. Here we demonstrated that skin injury increased the expression of IL-36γ to promote wound healing. Mechanistically, the expression of IL-36γ was induced by RNAs from damaged cells via the activation of Toll-like receptor 3 (TLR3) and TIR-domain-containing adapter-inducing interferon-β (TRIF) followed by the induction of a zinc finger protein SLUG to abrogate the inhibitory effect of vitamin D receptor (VDR) on the promoter of IL-36γ gene...
July 31, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28768728/extracellular-micrornas-induce-potent-innate-immune-responses-via-tlr7-myd88-dependent-mechanisms
#8
Yan Feng, Lin Zou, Dan Yan, Hongliang Chen, Ganqiong Xu, Wenling Jian, Ping Cui, Wei Chao
Tissue ischemia, such as transient myocardial ischemia, leads to release of cellular RNA including microRNA(miRNA) into the circulation and extracellular (ex-) space, but the biological function of the ex-RNA is poorly understood. We recently reported that cardiac RNA of both human and rodent origins induced cytokine production and immune cell activation. However, the identity of the ex-RNA responsible for the proinflammatory effect remains unclear. In the current study, using an miRNA array, we profiled the plasma miRNAs 4 h after transient myocardial ischemia (45 min) or sham procedure...
August 2, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28757610/the-il-1r-tlr-signaling-pathway-is-essential-for-efficient-cd8-t-cell-responses-against-hepatitis-b-virus-in-the-hydrodynamic-injection-mouse-model
#9
Zhiyong Ma, Jia Liu, Weimin Wu, Ejuan Zhang, Xiaoyong Zhang, Qian Li, Gennadiy Zelinskyy, Jan Buer, Ulf Dittmer, Carsten J Kirschning, Mengji Lu
The outcome of hepatitis B viral (HBV) infection is determined by the complex interactions between replicating HBV and the immune system. While the role of the adaptive immune system in the resolution of HBV infection has been studied extensively, the contribution of innate immune mechanisms remains to be defined. Here we examined the role of the interleukin-1 receptor/Toll-like receptor (IL-1R/TLR) signaling pathway in adaptive immune responses and viral clearance by exploring the HBV mouse model. Hydrodynamic injection with a replication-competent HBV genome was performed in wild-type mice (WT) and a panel of mouse strains lacking specific innate immunity component expression...
July 31, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28753906/dexmedetomidine-preconditioning-plays-a-neuroprotective-role-and-suppresses-tlr4-nf-%C3%AE%C2%BAb-pathways-model-of-cerebral-ischemia-reperfusion
#10
Shou-Liang Wang, Lian Duan, Bin Xia, Zhifei Liu, Yu Wang, Gong-Ming Wang
BACKGROUND: Dexmedetomidine has been reported to play an efficient role on multi-organ protection. Our study aims to investigate the neuroprotective of dexmedetomidine preconditioning on cerebral ischemic reperfusion (I/R) injury and investigate the underlining signaling mechanisms. METHODS: Cerebral I/R models were established with SD rats through middle cerebral artery occlusion (MCAO). After 2h of ischemia followed by 7days of reperfusion, the degree of cerebral tissue injury was detected by HE, Nissl and TUNEL staining...
September 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28750349/escherichia-coli-maltose-binding-protein-mbp-activates-mouse-th1-through-tlr2-mediated-myd88-dependent-pathway-and-tlr4-mediated-trif-dependent-pathway
#11
GuoMu Liu, YiXin Zhang, NanNan Zhang, WeiHua Ni, Jing Jie, LiNa Jiang, GuiXiang Tai
MBP (maltose-binding protein) is a component of Escherichia coli. Our previous study found that MBP directly induces the activation of Th1 (T helper type 1), but the molecular mechanism remains unclear. In the present study, CD4(+)T cells were purified from the spleens of normal mice using antibody-coated immunomagnetic beads by negative selection. CD4(+)T cells activated with a CD3/CD28 antibody were stimulated with MBP. The results indicated that MBP elevated IFN-γ mRNA levels in activated CD4(+)T cells and promoted IFN-γ production from activated CD4(+)T cells...
July 24, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28747347/trim8-negatively-regulates-tlr3-4-mediated-innate-immune-response-by-blocking-trif-tbk1-interaction
#12
Wen Ye, Ming-Ming Hu, Cao-Qi Lei, Qian Zhou, Heng Lin, Ming-Shun Sun, Hong-Bing Shu
TLR-mediated signaling pathways play critical roles in host defense against microbials. However, dysregulation of innate immune and inflammatory responses triggered by TLRs would result in harmful damage to the host. Using a Trim8 gene-knockout mouse model, we show that tripartite motif (TRIM) 8 negatively regulates TLR3- and TLR4-mediated innate immune and inflammatory responses. TRIM8 deficiency leads to increased polyinosinic-polycytidylic acid- and LPS-triggered induction of downstream anti-microbial genes including TNF, Il6, Rantes, and Ifnb, evaluated serum cytokine levels, and increased susceptibility of mice to polyinosinic-polycytidylic acid- and LPS-induced inflammatory death as well as Salmonella typhimurium infection-induced loss of body weight and septic shock...
July 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28736216/pathogen-induced-tlr4-trif-innate-immune-signaling-in-hematopoietic-stem-cells-promotes-proliferation-but-reduces-competitive-fitness
#13
Hitoshi Takizawa, Kristin Fritsch, Larisa V Kovtonyuk, Yasuyuki Saito, Chakradhar Yakkala, Kurt Jacobs, Akshay K Ahuja, Massimo Lopes, Annika Hausmann, Wolf-Dietrich Hardt, Álvaro Gomariz, César Nombela-Arrieta, Markus G Manz
Bacterial infection leads to consumption of short-lived innate immune effector cells, which then need to be replenished from hematopoietic stem and progenitor cells (HSPCs). HSPCs express pattern recognition receptors, such as Toll-like receptors (TLRs), and ligation of these receptors induces HSPC mobilization, cytokine production, and myeloid differentiation. The underlying mechanisms involved in pathogen signal transduction in HSCs and the resulting biological consequences remain poorly defined. Here, we show that in vivo lipopolysaccharide (LPS) application induces proliferation of dormant HSCs directly via TLR4 and that sustained LPS exposure impairs HSC self-renewal and competitive repopulation activity...
August 3, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28733470/dendritic-cell-targeted-lentiviral-vector-immunization-uses-pseudotransduction-and-dna-mediated-sting-and-cgas-activation
#14
Jocelyn T Kim, Yarong Liu, Rajan P Kulkarni, Kevin K Lee, Bingbing Dai, Geoffrey Lovely, Yong Ouyang, Pin Wang, Lili Yang, David Baltimore
Dendritic cell (DC) activation and antigen presentation are critical for efficient priming of T cell responses. Here, we study how lentiviral vectors (LVs) deliver antigen and activate DCs to generate T cell immunization in vivo. We report that antigenic proteins delivered in vector particles via pseudotransduction were sufficient to stimulate an antigen-specific immune response. The delivery of the viral genome encoding the antigen increased the magnitude of this response in vivo but was irrelevant in vitro...
July 21, 2017: Science Immunology
https://www.readbyqxmd.com/read/28729359/the-%C3%AE-defensin-retrocyclin-101-inhibits-tlr4-and-tlr2-dependent-signaling-and-protects-mice-against-influenza-infection
#15
Daniel Prantner, Kari Ann Shirey, Wendy Lai, Wuyuan Lu, Alexander M Cole, Stefanie N Vogel, Alfredo Garzino-Demo
Despite widespread use of annual influenza vaccines, seasonal influenza-associated deaths number in the thousands each year, in part because of exacerbating bacterial superinfections. Therefore, discovering additional therapeutic options would be a valuable aid to public health. Recently, TLR4 inhibition has emerged as a possible mechanism for protection against influenza-associated lethality and acute lung injury. Based on recent data showing that rhesus macaque θ-defensins could inhibit TLR4-dependent gene expression, we tested the hypothesis that a novel θ-defensin, retrocyclin (RC)-101, could disrupt TLR4-dependent signaling and protect against viral infection...
July 20, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28723569/xiap-loss-triggers-ripk3-and-caspase-8-driven-il-1%C3%AE-activation-and-cell-death-as-a-consequence-of-tlr-myd88-induced-ciap1-traf2-degradation
#16
Kate E Lawlor, Rebecca Feltham, Monica Yabal, Stephanie A Conos, Kaiwen W Chen, Stephanie Ziehe, Carina Graß, Yifan Zhan, Tan A Nguyen, Cathrine Hall, Angelina J Vince, Simon M Chatfield, Damian B D'Silva, Kenneth C Pang, Kate Schroder, John Silke, David L Vaux, Philipp J Jost, James E Vince
X-linked Inhibitor of Apoptosis (XIAP) deficiency predisposes people to pathogen-associated hyperinflammation. Upon XIAP loss, Toll-like receptor (TLR) ligation triggers RIPK3-caspase-8-mediated IL-1β activation and death in myeloid cells. How XIAP suppresses these events remains unclear. Here, we show that TLR-MyD88 causes the proteasomal degradation of the related IAP, cIAP1, and its adaptor, TRAF2, by inducing TNF and TNF Receptor 2 (TNFR2) signaling. Genetically, we define that myeloid-specific cIAP1 loss promotes TLR-induced RIPK3-caspase-8 and IL-1β activity in the absence of XIAP...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28717003/surface-toll-like-receptor-3-expression-in-metastatic-intestinal-epithelial-cells-induces-inflammatory-cytokine-production-and-promotes-invasiveness
#17
Marit Bugge, Bjarte Bergstrom, Oda Kamilla Eide, Helene Solli, Ingrid F Kjønstad, Jørgen Stenvik, Terje Espevik, Nadra J Nilsen
Toll-like receptors (TLR)s are innate immune receptors for sensing microbial molecules and damage-associated molecular patterns released from host cells. Double-stranded RNA and the synthetic analog polyinosinic:polycytidylic acid (Poly(I:C)) bind and activate TLR3. This stimulation leads to recruitment of the adaptor molecule TRIF and activation of the transcription factors nuclear factor κB (NF-κB) and interferon regulatory factor 3 (IRF-3), classically inducing IFNβ production. Here, we report that unlike non-metastatic intestinal epithelial cells (IECs), metastatic IECs express TLR3, and that TLR3 promotes invasiveness of these cells...
July 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28695368/an-interaction-of-lps-and-rsv-infection-in-augmenting-the-ahr-and-airway-inflammation-in-mice
#18
Na Zhou, Wei Li, Luo Ren, Xiaohong Xie, Enmei Liu
Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infection (LRTI) in children under 5 years of age, especially infants with severe bronchiolitis. Our preliminary clinical experiments showed that bacterial colonization was commonly observed in children with virus-induced wheezing, particularly in those with recurrent wheezing, suggesting that bacterial colonization with an accompanying viral infection may contribute to disease severity. In most cases, RSV-infected infants were colonized with pathogenic bacteria (mainly Gram-negative bacteria)...
July 10, 2017: Inflammation
https://www.readbyqxmd.com/read/28670876/autophagy-regulates-apoptosis-on-the-level-of-the-death-inducing-signalling-complex
#19
Karin Nowikovsky, Michael Bergmann
The interactions between apoptotic and autophagic proteins via the proteolytic systems are known mechanisms through which autophagy and apoptosis regulate each other. In this issue of The FEBS Journal, Gentle and colleagues propose a mechanism through which autophagy regulates the induction of apoptosis at the level of the TIR-domain-containing adaptor-inducing interferon-β (TRIF) in TLR signaling.
July 2017: FEBS Journal
https://www.readbyqxmd.com/read/28669384/differences-in-expression-of-genes-in-the-myd88-and-trif-signalling-pathways-and-methylation-of-tlr4-and-trif-in-tibetan-chickens-and-daheng-s03-chickens-infected-with-salmonella-enterica-serovar-enteritidis
#20
Xiaocheng Li, Peng Zhang, Xiaosong Jiang, Huarui Du, Chaowu Yang, Zengrong Zhang, Shuai Men, Zhikun Zhang, Wei Jiang, Hongning Wang
Salmonella enterica serovar (S. enteritidis) is a pathogenic bacterium that can cause symptoms of food poisoning, leading to death of poultry, resulting in serious economic losses. The MyD88 and TRIF signalling pathways play important roles in activating innate and adaptive immunity in chickens infected with S. enteritidis. The objective of the present study was to characterize in vivo mRNA expressions, protein levels and methylation levels of genes in the above two pathways in both Tibetan chickens and DaHeng S03 chickens infected with S...
July 2017: Veterinary Immunology and Immunopathology
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