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https://www.readbyqxmd.com/read/28747574/oridonin-attenuates-the-release-of-pro-inflammatory-cytokines-in-lipopolysaccharide-induced-raw264-7-cells-and-acute-lung-injury
#1
Gan Zhao, Tao Zhang, Xiaofei Ma, Kangfeng Jiang, Haichong Wu, Changwei Qiu, Mengyao Guo, Ganzhen Deng
Acute lung injury (ALI) is a life-threatening inflammatory disease owing to the lack of specific and effective therapies. Oridonin (Ori) is an active diterpenoid isolated from Rabdosiarubescens (R.rubescens) that has been shown to possess a broadspectrum pharmacological properties including anti-inflammatory, antitumour, antioxidative and neuroregulatory effects. However, its potential protective mechanism in ALI is not well characterized. In this study, we demonstrated that Ori reduces the mortality of mice with ALI induced by a high dose of lipopolysaccharide (LPS), which suggests that Ori has a protective effect on LPS induced ALI...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28747343/the-development-of-steady-state-activation-hubs-between-adult-lti-ilc3s-and-primed-macrophages-in-small-intestine
#2
Adam K Savage, Hong-Erh Liang, Richard M Locksley
Group 3 innate lymphoid cells (ILC3s) are important for intestinal health, particularly in controlling inflammation in response to epithelial dysregulation, but their role during homeostasis remains less well understood. We generated IL-22 reporter mice to assess production of this key cytokine by ILC3s in the small intestine during development and under basal conditions. Although IL-22 is produced by a variety of lymphocyte populations, constitutively high IL-22 expression was limited to lymphoid-tissue inducer (LTi) cells residing in lymph node-like structures in the gut called solitary intestinal lymphoid tissues (SILT)...
July 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28739828/mice-bone-marrow-sca-1-cd44-mesenchymal-stem-cells-kill-avirulent-mycobacteria-but-not-mycobacterium-tuberculosis-through-modulation-of-cathelicidin-expression-via-p38-mapk-dependent-pathway
#3
Sumanta Kumar Naik, Avinash Padhi, Geetanjali Ganguli, Srabasti Sengupta, Sanghamitra Pati, Dasarathi Das, Avinash Sonawane
Mycobacterium tuberculosis (Mtb) primarily infects lung macrophages. However, recent study has shown that Mtb also infect and persist in dormant form inside the bone marrow mesenchymal stem cells (BM-MSCs) even after successful antibiotic therapy. However, the mechanism(s) by which Mtb survives in BM-MSCs is still not known. Like macrophages, BM-MSCs do not contain a well-defined endocytic pathway, which is known to play a central role in the clearance of internalized mycobacteria. Here, we studied the fate of virulent and avirulent mycobacteria in Sca-1(+)/CD44(+) BM-MSCs...
July 24, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28736216/pathogen-induced-tlr4-trif-innate-immune-signaling-in-hematopoietic-stem-cells-promotes-proliferation-but-reduces-competitive-fitness
#4
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...
July 19, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28735521/myd88-erk-nfkb%C3%A2-pathways-and-pro-inflammatory-cytokines-release-in-periodontal-ligament-stem-cells-stimulated-by-porphyromonas%C3%A2-gingivalis
#5
Francesca Diomede, Maria Zingariello, Marcos F X B Cavalcanti, Ilaria Merciaro, Jacopo Pizzicannella, Natalia De Isla, Sergio Caputi, Patrizia Ballerini, Oriana Trubiani
The present study was aimed at investigating whether human Periodontal Ligament Stem Cells (hPDLSCs) were capable of sensing and reacting to lipopolysaccharide from Porphyromonas gingivalis (LPS-G) which is widely recognized as a major pathogen in the development and progression of periodontitis. At this purpose hPDLCs were stimulated with 5 μg/mL LPS-G various times and the expression of toll-like receptor 4 (TLR4) was evaluated. Toll-like receptors (TLRs) play an essential role in innate immune signaling in response to microbial infections, and in particular TLR4, type-I transmembrane proteins, has been shown recognizing LPS-G...
May 24, 2017: European Journal of Histochemistry: EJH
https://www.readbyqxmd.com/read/28733486/%C3%AE-toxin-regulates-local-granulocyte-expansion-from-hematopoietic-stem-and-progenitor-cells-in-staphylococcus-aureus-infected-wounds
#6
Patrick C Falahee, Leif S Anderson, Mack B Reynolds, Mauricio Pirir, Bridget E McLaughlin, Carly A Dillen, Ambrose L Cheung, Lloyd S Miller, Scott I Simon
The immune response to Staphylococcus aureus infection in skin involves the recruitment of polymorphonuclear neutrophils (PMNs) from the bone marrow via the circulation and local granulopoiesis from hematopoietic stem and progenitor cells (HSPCs) that also traffic to infected skin wounds. We focus on regulation of PMN number and function and the role of pore-forming α-toxin (AT), a virulence factor that causes host cell lysis and elicits inflammasome-mediated IL-1β secretion in wounds. Infection with wild-type S...
July 21, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28733470/dendritic-cell-targeted-lentiviral-vector-immunization-uses-pseudotransduction-and-dna-mediated-sting-and-cgas-activation
#7
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
#8
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/28725012/phycocyanin-attenuates-pulmonary-fibrosis-via-the-tlr2-myd88-nf-%C3%AE%C2%BAb-signaling-pathway
#9
Chengcheng Li, Yan Yu, Wenjun Li, Bo Liu, Xudong Jiao, Xinyu Song, Changjun Lv, Song Qin
Our aim was to investigate the effects of phycocyanin (PC) on bleomycin (BLM)-induced pulmonary fibrosis (PF). In this study, C57 BL/6 wild-type (WT) mice and toll-like receptor (TLR) 2 deficient mice were treated with PC for 28 days following BLM exposure. Serum and lung tissues were collected on days 3, 7 and 28. Data shows PC significantly decreased the levels of hydroxyproline (HYP), vimentin, surfactant-associated protein C (SP-C), fibroblast specific protein-1 (S100A4) and α-smooth muscle actin (α-SMA) but dramatically increased E-cadherin and podoplanin (PDPN) expression on day 28...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724768/synthetic-tlr4-and-tlr7-ligands-work-additively-via-myd88-to-induce-protective-antiviral-immunity-in-mice
#10
Peter H Goff, Tomoko Hayashi, Wenqian He, Shiyin Yao, Howard B Cottam, Gene S Tan, Brian Crain, Florian Krammer, Karen Messer, Minya Pu, Dennis A Carson, Peter Palese, Maripat Corr
We have previously demonstrated that the combination of synthetic small molecule Toll-like receptor 4 (TLR4) and TLR7 ligands is a potent adjuvant for recombinant influenza virus hemagglutinin, inducing rapid and sustained immunity protective against influenza viruses in homologous, heterologous and heterosubtypic murine challenge models. Combining TLR4 and TLR7 ligands balances Th1/Th2-type immune responses for long-lived cellular and neutralizing humoral immunity against the viral hemagglutinin. Here, we demonstrate that the protective response induced in mice by this combined adjuvant is dependent upon TLR4 and TLR7 signaling via myeloid differentiation primary response gene 88 (MyD88), indicating that the adjuvants function in vivo via their known receptors with negligible off-target effects to induce protective immunity...
July 19, 2017: Journal of Virology
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
#11
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/28712404/-polymorphisms-of-tlr7-rs3853839-and-rs179010-are-associated-with-susceptibility-to-and-severity-of-hand-foot-and-mouth-disease-caused-by-enterovirus-71-in-male-children
#12
Yaping Li, Song Zhai, Mei Li, Yuan Wang, Tong Lu, Huiling Deng, Xin Zhang, Shuangsuo Dang
Objective To investigate whether the polymorphisms of TLR7/MyD88 signaling pathway is associated with the susceptibility to and severity of hand, foot and mouth disease (HFMD) caused by enterovirus 71 (EV71) in children. Methods We collected 180 EV71 HFMD cases and 201 healthy controls from both the Second Affiliated Hospital of Xi'an Jiaotong University and Xi'an Children's Hospital. The genotypes including rs3853839, rs179010 of TLR7, and rs7744 of MyD88 were detected in the 381 samples by SNPscan kit. Results The susceptibility risk (OR=2...
July 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28711031/the-sinomenine-enteric-coated-microspheres-suppressed-the-tlr-nf-%C3%AE%C2%BAb-signaling-in-dss-induced-experimental-colitis
#13
Huifang Xiong, Liang Tian, Zihan Zhao, Shuping Chen, Qiaoyun Zhao, Junbo Hong, Yong Xie, Nanjin Zhou, Yingjun Fu
Sinomenine is a pure alkaloid with immunosuppressive effects that is extracted from the Chinese medicinal plant Sinomenium acutum. We studied the therapeutic effects of sinomenine on inflammatory bowel disease. In this study, we randomly divided mice into the following ten groups: Control group; DSS-induced colitis group; Salicylazosulfapyridine (SASP)-treated group; Chitosan-treated group; low-, medium-, and high-dose sinomenine-treated and sinomenine enteric-coated microspheres-treated groups. We recorded changes in colon length, disease activity index (DAI), and colon pathology, measured TLR4, MyD88, SIGIRR, NF-κB p65 protein levels and inflammatory serum cytokine levels...
July 12, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28706459/beauvericin-a-cyclic-peptide-inhibits-inflammatory-responses-in-macrophages-by-inhibiting-the-nf-%C3%AE%C2%BAb-pathway
#14
Sulgi Yoo, Mi-Yeon Kim, Jae Youl Cho
Beauvericin (BEA), a cyclic hexadepsipeptide produced by the fungus Beauveria bassiana, is known to have anti-cancer, anti-inflammatory, and anti-microbial actions. However, how BEA suppresses macrophage-induced inflammatory responses has not been fully elucidated. In this study, we explored the anti-inflammatory properties of BEA and the underlying molecular mechanisms using lipopolysaccharide (LPS)-treated macrophage-like RAW264.7 cells. Levels of nitric oxide (NO), mRNA levels of transcription factors and the inflammatory genes inducible NO synthase (iNOS) and interleukin (IL)-1, and protein levels of activated intracellular signaling molecules were determined by Griess assay, semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), luciferase reporter gene assay, and immunoblotting analysis...
July 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28706136/swine-irf3-irf7-attenuates-inflammatory-responses-through-tlr4-signaling-pathway
#15
Pei-Ge Chen, Yan-Jing Guan, Guang-Ming Zha, Xian-Qin Jiao, He-Shui Zhu, Cheng-Yu Zhang, Yue-Ying Wang, He-Ping Li
To explore the role of IRF3/IRF7 during inflammatory responses, we investigated the effects of swine IRF3/IRF7 on TLR4 signaling pathway and inflammatory factors expression in porcine kidney epithelial PK15 cell lines. We successfully constructed eukaryotic vectors PB-IRF3 and PB-IRF7, transfected these vectors into PK15 cells and observed GFP under a fluorescence microscope. In addition, RT-PCR was also used to detect transfection efficiency. We found that IRF3/IRF7 was efficiently overexpressed in PK15 cells...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28704651/synergy-between-the-host-immune-system-and-bacteriophage-is-essential-for-successful-phage-therapy-against-an-acute-respiratory-pathogen
#16
Dwayne R Roach, Chung Yin Leung, Marine Henry, Eric Morello, Devika Singh, James P Di Santo, Joshua S Weitz, Laurent Debarbieux
The rise of multi-drug-resistant (MDR) bacteria has spurred renewed interest in the use of bacteriophages in therapy. However, mechanisms contributing to phage-mediated bacterial clearance in an animal host remain unclear. We investigated the effects of host immunity on the efficacy of phage therapy for acute pneumonia caused by MDR Pseudomonas aeruginosa in a mouse model. Comparing efficacies of phage-curative and prophylactic treatments in healthy immunocompetent, MyD88-deficient, lymphocyte-deficient, and neutrophil-depleted murine hosts revealed that neutrophil-phage synergy is essential for the resolution of pneumonia...
July 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28704394/genome-wide-host-gene-expression-analysis-in-mice-experimentally-infected-with-pasteurella-multocida
#17
G Bhuvana Priya, Viswas Konasagara Nagaleekar, A Arun Prince Milton, M Saminathan, Amod Kumar, Amit Ranjan Sahoo, Sajad Ahmad Wani, Amit Kumar, S K Gupta, Aditya P Sahoo, A K Tiwari, R K Agarwal, Ravi Kumar Gandham
Pasteurella multocida causes acute septicemic and respiratory diseases, including haemorrhagic septicaemia, in cattle and buffalo with case fatality of 100%. In the present study, mice were infected with P. multocida (1.6 × 103 cfu, intraperitoneal) to evaluate host gene expression profile at early and late stages of infection using high throughput microarray transcriptome analyses. Several differentially expressed genes (DEGs) at both the time points were identified in P.multocida infected spleen, liver and lungs...
2017: PloS One
https://www.readbyqxmd.com/read/28701369/synergistic-cooperation-and-crosstalk-between-myd88-l265p-and-mutations-that-dysregulate-cd79b-and-surface-igm
#18
James Q Wang, Yogesh S Jeelall, Peter Humburg, Emma L Batchelor, Sarp M Kaya, Hee Min Yoo, Christopher C Goodnow, Keisuke Horikawa
CD79B and MYD88 mutations are frequently and simultaneously detected in B cell malignancies. It is not known if these mutations cooperate or how crosstalk occurs. Here we analyze the consequences of CD79B and MYD88(L265P) mutations individually and combined in normal activated mouse B lymphocytes. CD79B mutations alone increased surface IgM but did not enhance B cell survival, proliferation, or altered NF-κB responsive markers. Conversely, B cells expressing MYD88(L265P) decreased surface IgM coupled with accumulation of endoglycosidase H-sensitive IgM intracellularly, resembling the trafficking block in anergic B cells repeatedly stimulated by self-antigen...
July 12, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28698147/rip2-deficiency-attenuates-cardiac-hypertrophy-inflammation-and-fibrosis-in-pressure-overload-induced-mice
#19
Cui-Hua Zhao, Xiang Ma, Hong-Yu Guo, Peng Li, Hong-Yang Liu
Although the pathological cardiac hypertrophy presents a leading cause of morbidity and mortality worldwide, our knowledge of the molecular mechanisms underlying the disease is still poor. Here, we reported that receptor-interacting serine/threonine-protein kinase 2 (RIP2), promoting pro-inflammatory gene expression, enhanced the pathological cardiac hypertrophy in animals. The effects of RIP2 on the cardiac hypertrophy triggered by pathological stimuli have not been fully investigated. In our study, mice were subjected to aortic banding (AB) surgery to explore the pathological, echocardiographic and molecular mechanisms...
July 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28697888/regulated-expansion-and-survival-of-chimeric-antigen-receptor-modified-t-cells-using-small-molecule-dependent-inducible-myd88-cd40
#20
Aaron E Foster, Aruna Mahendravada, Nicholas P Shinners, Wei-Chun Chang, Jeannette Crisostomo, An Lu, Mariam Khalil, Eva Morschl, Joanne L Shaw, Sunandan Saha, MyLinh T Duong, Matthew R Collinson-Pautz, David L Torres, Tania Rodriguez, Tsvetelina Pentcheva-Hoang, J Henri Bayle, Kevin M Slawin, David M Spencer
Anti-tumor efficacy of T cells engineered to express chimeric antigen receptors (CARs) is dependent on their specificity, survival, and in vivo expansion following adoptive transfer. Toll-like receptor (TLR) and CD40 signaling in T cells can improve persistence and drive proliferation of antigen-specific CD4(+) and CD8(+) T cells following pathogen challenge or in graft-versus-host disease (GvHD) settings, suggesting that these costimulatory pathways may be co-opted to improve CAR-T cell persistence and function...
July 8, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
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