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https://www.readbyqxmd.com/read/29353310/nod-like-receptor-s-and-host-immune-responses-with-pseudomonas-aeruginosa-infection
#1
REVIEW
Alaa Alhazmi
INTRODUCTION: Molecular mechanisms underlying the interactions between Pseudomonas aeruginosa, the common opportunistic pathogen in cystic fibrosis individuals, and host induce a number of marked inflammatory responses and associate with complex therapeutic problems due to bacterial resistance to antibiotics in chronic stage of infection. METHODS: Pseudomonas aeruginosa is recognized by number of pattern recognition receptors (PRRs); NOD-like receptors (NLRs) are a class of PRRs, which can recognize a variety of endogenous and exogenous ligands, thereby playing a critical role in innate immunity...
January 20, 2018: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/29352876/structural-characterization-and-macrophage-activation-of-a-hetero-galactan-isolated-from-flammulina-velutipes
#2
Yue Meng, Jingmin Yan, Guang Yang, Zhen Han, Guihua Tai, Hairong Cheng, Yifa Zhou
We isolated and purified a new polysaccharide (WFVP-N-b1) with a molecular weight of 20 kDa from Flammulina velutipes. Results showed that WFVP-N-b1 is composed of an α (1 → 6)-linked D-galactan backbone and branched at the O-2 of its Galp residues by an α-D-(1 → 6)-linked Manp attached to t-β-D-Glcp or t-α-D-Fucp side chains. WFVP-N-b1 can significantly induce cytokines secretion and release of toxic molecules. On a cellular level, WFVP-N-b1 is recognized by Toll-like receptor 4 (TLR4). Thereby, the hetero-galactan increased the phosphorylation of mitogen-activated protein kinases (MAPKs) and Akt, promoted degradation of IκB-α and the nuclear translocation of the NF-κB p65 subunit...
March 1, 2018: Carbohydrate Polymers
https://www.readbyqxmd.com/read/29352742/cambogin-suppresses-dextran-sulphate-sodium-induced-colitis-by-enhancing-treg-cell-stability-and-function
#3
Yue Lu, Na-Mi Kim, Yi-Wen Jiang, Hong Zhang, Dan Zheng, Fu-Xiang Zhu, Rui Liang, Bin Li, Hong-Xi Xu
BACKGROUND AND PURPOSE: Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of gastrointestinal tract, and the dysfunction of immune regulation plays a critical role in IBD. Reflecting the limited use of current drugs and therapies for IBD treatment, it is necessary to explore novel drugs or therapies for this disease. We investigated the effect of cambogin in a mouse model of dextran sulphate sodium (DSS)-induced colitis and whether cambogin attenuates inflammation via Treg-cell-mediated immune modulation...
January 20, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29352287/ifn%C3%AE-inhibits-g-csf-induced-neutrophil-expansion-and-invasion-of-the-cns-to-prevent-viral-encephalitis
#4
Chandran Ramakrishna, Edouard M Cantin
Emergency hematopoiesis facilitates the rapid expansion of inflammatory immune cells in response to infections by pathogens, a process that must be carefully regulated to prevent potentially life threatening inflammatory responses. Here, we describe a novel regulatory role for the cytokine IFNγ that is critical for preventing fatal encephalitis after viral infection. HSV1 encephalitis (HSE) is triggered by the invasion of the brainstem by inflammatory monocytes and neutrophils. In mice lacking IFNγ (GKO), we observed unrestrained increases in G-CSF levels but not in GM-CSF or IL-17...
January 19, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29352207/ethanol-sensitizes-hepatocytes-for-tgf-%C3%AE-triggered-apoptosis
#5
Haristi Gaitantzi, Christoph Meyer, Pia Rakoczy, Maria Thomas, Kristin Wahl, Franziska Wandrer, Heike Bantel, Hamed Alborzinia, Stefan Wölfl, Sabrina Ehnert, Andreas Nüssler, Ina Bergheim, Loredana Ciuclan, Matthias Ebert, Katja Breitkopf-Heinlein, Steven Dooley
Alcohol abuse is a global health problem causing a substantial fraction of chronic liver diseases. Abundant TGF-β-a potent pro-fibrogenic cytokine-leads to disease progression. Our aim was to elucidate the crosstalk of TGF-β and alcohol on hepatocytes. Primary murine hepatocytes were challenged with ethanol and TGF-β and cell fate was determined. Fluidigm RNA analyses revealed transcriptional effects that regulate survival and apoptosis. Mechanistic insights were derived from enzyme/pathway inhibition experiments and modulation of oxidative stress levels...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352133/molecular-and-physiological-roles-of-the-adaptor-protein-card9-in-immunity
#6
REVIEW
Xiaoming Zhong, Bin Chen, Liang Yang, Zhiwen Yang
CARD9 is a caspase recruitment domain-containing signaling protein that plays a critical role in innate and adaptive immunity. It has been widely demonstrated that CARD9 adaptor allows pattern recognition receptors to induce NF-κB and MAPK activation, which initiates a "downstream" inflammation cytokine cascade and provides effective protection against microbial invasion, especially fungal infection. Here our aim is to update existing paradigms and summarize the most recent findings on the CARD9 signaling pathway, revealing significant mechanistic insights into the pathogenesis of CARD9 deficiency...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352108/desumoylation-of-mkk7-kinase-by-the-sumo2-3-protease-senp3-potentiates-lipopolysaccharide-induced-inflammatory-signaling-in-macrophages
#7
Yimin Lao, Kai Yang, Zhaojun Wang, Xueqing Sun, Qiang Zou, Xiaoyan Yu, Jinke Cheng, Xuemei Tong, Edward Th Yeh, Jie Yang, Jing Yi
Protein SUMOylation has been reported to play a role in innate immune response, but the enzymes, substrates, and consequences of the specific inflammatory signaling events are largely unknown. Reactive oxygen species (ROS) are abundantly produced during macrophage activation and required for Toll-like receptor 4 (TLR4)-mediated inflammatory signaling. Previously, we demonstrated that SENP3 is a redox-sensitive SUMO2/3 protease. To explore any links between reversible SUMOylation and ROS-related inflammatory signaling in macrophage activation, we generated mice with SENP3 conditional knockout in myeloid cells...
January 19, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29351913/the-rig-i-like-receptor-lgp2-inhibits-dicer-dependent-processing-of-long-double-stranded-rna-and-blocks-rna-interference-in-mammalian-cells
#8
Annemarthe G van der Veen, Pierre V Maillard, Jan Marten Schmidt, Sonia A Lee, Safia Deddouche-Grass, Annabel Borg, Svend Kjær, Ambrosius P Snijders, Caetano Reis E Sousa
In vertebrates, the presence of viral RNA in the cytosol is sensed by members of the RIG-I-like receptor (RLR) family, which signal to induce production of type I interferons (IFN). These key antiviral cytokines act in a paracrine and autocrine manner to induce hundreds of interferon-stimulated genes (ISGs), whose protein products restrict viral entry, replication and budding. ISGs include the RLRs themselves: RIG-I, MDA5 and, the least-studied family member, LGP2. In contrast, the IFN system is absent in plants and invertebrates, which defend themselves from viral intruders using RNA interference (RNAi)...
January 19, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29351902/targeting-the-sphk1-s1p-s1pr1-axis-that-links-obesity-chronic-inflammation-and-breast-cancer-metastasis
#9
Masayuki Nagahashi, Akimitsu Yamada, Eriko Katsuta, Tomoyoshi Aoyagi, Wei-Ching Huang, Krista P Terracina, Nitai C Hait, Jeremy C Allegood, Junko Tsuchida, Kizuki Yuza, Masato Nakajima, Manabu Abe, Kenji Sakimura, Sheldon Milstien, Toshifumi Wakai, Sarah Spiegel, Kazuaki Takabe
Although obesity with associated inflammation is now recognized as a risk factor for breast cancer and distant metastases, the functional basis for these connections remain poorly understood. Here we show that in breast cancer patients and in animal breast cancer models, obesity is a sufficient cause for increased expression of the bioactive sphingolipid mediator sphingosine-1-phosphate (S1P) which mediates cancer pathogenesis. A high fat diet was sufficient to upregulate expression of sphingosine kinase 1 (SphK1), the enzyme that produces S1P, along with its receptor S1PR1 in syngeneic and spontaneous breast tumors...
January 19, 2018: Cancer Research
https://www.readbyqxmd.com/read/29351816/effects-of-gut-derived-endotoxin-on-anxiety-like-and-repetitive-behaviors-in-male-and-female-mice
#10
Christopher T Fields, Benoit Chassaing, Alexandra Castillo-Ruiz, Remus Osan, Andrew T Gewirtz, Geert J de Vries
BACKGROUND: Gut dysbiosis is observed in several neuropsychiatric disorders exhibiting increases in anxiety behavior, and recent work suggests links between gut inflammation and such disorders. One source of this inflammation may be lipopolysaccharide (LPS), a toxic component of gram-negative bacteria. Here, we (1) determine whether oral gavage of LPS, as a model of gut-derived endotoxemia, affects anxiety-like and/or repetitive behaviors; (2) test whether these changes depend on TLR4 signaling; and (3) test the extent to which gut-derived endotoxin and TLR4 antagonism affects males and females differently...
January 19, 2018: Biology of Sex Differences
https://www.readbyqxmd.com/read/29351747/combination-of-pelargonium-sidoides-and-coptis-chinensis-root-inhibits-nuclear-factor-kappa-b-mediated-inflammatory-response-in-vitro-and-in-vivo
#11
Sang Mi Park, Byung-Gu Min, Ji Yun Jung, Kyung Hwan Jegal, Chul Won Lee, Kwang Youn Kim, Young Woo Kim, Youn-Woong Choi, Il Je Cho, Sae Kwang Ku, Sang Chan Kim
BACKGROUND: Pelargonium sidoides (PS) and Coptis chinensis root (CR) have traditionally been used to treat various diseases, including respiratory and gastrointestinal infections, dysmenorrhea, and hepatic disorders. The present study was conducted to evaluate the anti-inflammatory effects of a combination of PS and CR in vitro and in vivo. METHODS: The in vitro effects of PS + CR on the induction of inflammation-related proteins were evaluated in lipopolysaccharide (LPS)-stimulated RAW 264...
January 19, 2018: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/29351448/extracellular-oxidation-in-cystic-fibrosis-airway-epithelium-causes-enhanced-egfr-adam17-activity
#12
Marta Stolarczyk, Guido Veit, Andrea Schnur, Mieke Veltman, Gergely L Lukacs, Bob J Scholte
The EGFR/ADAM17 signaling pathway mediates the shedding of growth factors and secretion of cytokines, and is involved in chronic inflammation and tissue remodeling. Since these are hallmarks of cystic fibrosis (CF) lung disease, we hypothesized that CFTR deficiency enhances EGFR/ADAM17 activity in human bronchial epithelial cells. In CFBE41o- cells lacking functional CFTR (iCFTR-) cultured at air-liquid interface (ALI) we found enhanced ADAM17-mediated shedding of the EGFR ligand amphiregulin (AREG) compared to genetically identical cells with induced CFTR expression (iCFTR+)...
December 14, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29351434/cub-domain-containing-protein-1-cdcp1-negatively-regulates-tgf%C3%AE-signaling-and-myofibroblast-differentiation
#13
Nina Noskovičová, Katharina Heinzelmann, Gerald Burgstaller, Jürgen Behr, Oliver Eickelberg
Fibroblasts are thought to be the prime cell type for producing and secreting extracellular matrix (ECM) proteins in the connective tissue. The profibrotic cytokine, transforming growth factor-beta 1 (TGFβ1) activates and transdifferentiates fibroblasts into αSMA-expressing myofibroblasts, which exhibit increased ECM secretion, in particular collagens. Little information, however, exists about cell-surface molecules on fibroblasts that mediate this transdifferentiation process. We recently identified, using unbiased cell-surface proteome analysis, Cub domain containing protein 1 (CDCP1) to be strongly downregulated by TGFβ1...
January 4, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29351125/central-inhibition-of-granulocyte-macrophage-colony-stimulating-factor-is-analgesic-in-experimental-neuropathic-pain
#14
Louise S C Nicol, Peter Thornton, Jon P Hatcher, Colin P Glover, Carl I Webster, Matthew Burrell, Kessia Hammett, Clare A Jones, Matthew A Sleeman, Andrew Billinton, Iain Chessell
With less than 50% of patients responding to the current standard of care and poor efficacy and selectivity of current treatments, neuropathic pain continues to be an area of considerable unmet medical need. Biological therapeutics such as monoclonal antibodies (mAbs) provide better intrinsic selectivity; however, delivery to the central nervous system (CNS) remains a challenge. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is well described in inflammation-induced pain, and early-phase clinical trials evaluating its antagonism have exemplified its importance as a peripheral pain target...
January 16, 2018: Pain
https://www.readbyqxmd.com/read/29350876/mechanism-of-mer-receptor-tyrosine-kinase-inhibition-of-glomerular-endothelial-cell-inflammation
#15
Yuxuan Zhen, Fred D Finkelman, Wen-Hai Shao
Endotoxin induces a variety of proinflammatory mediators and plays a crucial role in kidney inflammation. The receptor tyrosine kinase, Mer, diminishes renal inflammation by attenuating inflammatory responses. We previously reported that Mer is predominantly expressed on glomerular endothelial cells (GECs) and that Mer deficiency is associated with increased renal inflammation when mice are challenged with nephrotoxic serum. We consequently hypothesized that Mer signaling down-regulates LPS-driven inflammatory responses in GECs...
January 19, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29350834/proton-pump-inhibitors-elevate-infection-rate-in-cardiothoracic-surgery-patients-by-influencing-pmn-function-in-vitro-and-in-vivo
#16
Carolin Maria Haas, Martina Maywald, Andreas Goetzenich, Christian Stoppe, Lothar Rink
Proton-pump inhibitors (PPI) as pantoprazole are highly effective acid suppressive agents that belong to the world's most sold medication. However, they are pronounced to have immunosuppressive aspects. In our study, a negative influence of PPI on functions of polymorphonuclear cells in vitro like phagocytosis, oxidative burst, chemotaxis, and killing activity was shown, whereas formation of neutrophil extracellular traps (NET)osis remained unaffected. Pantoprazole stimulation additionally reduced the production of the proinflammatory cytokine IL-1β in whole blood assay as well as the production of IL-2 and IFN-γ after whole blood stimulation with phytohaemagglutinin...
January 19, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29350807/mait-cells-and-viruses
#17
James E Ussher, Christian B Willberg, Paul Klenerman
Mucosal associated invariant T cells (MAIT cells) bear a T cell receptor (TCR) that specifically targets microbially-derived metabolites. Functionally they respond to bacteria and yeasts, which possess the riboflavin pathway, essential for production of such metabolites and which are presented on MR1. Viruses cannot generate these ligands, so a priori, they should not be recognized by MAIT cells and indeed this is true when considering recognition through the TCR. However, MAIT cells are distinctive in another respect, since they respond quite sensitively to non-TCR signals, especially in the form of inflammatory cytokines...
January 19, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29350049/targeted-and-off-target-bystander-and-abscopal-effects-of-radiation-therapy-redox-mechanisms-and-risk-benefit-analysis
#18
Jean-Pierre Pouget, Alexandros G Georgakilas, Jean-Luc Ravanat
Radiation therapy (from external beams to unsealed and sealed radionuclide sources) takes advantage of the detrimental effects of the clustered production of radicals and reactive oxygen species (ROS). Research has mainly focused on the interaction of radiation with water, which is the major constituent of living beings, and with nuclear DNA, which contains the genetic information. This led to the so-called "target" theory according to which cells have to be hit by ionizing particles to elicit an important biological response, including cell death...
January 19, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29349774/the-vaccine-adjuvant-alum-promotes-il-10-production-that-suppresses-th1-responses
#19
Ewa Oleszycka, Sean McCluskey, Fiona A Sharp, Natalia Muñoz-Wolf, Emily Hams, Aoife L Gorman, Padraic G Fallon, Ed C Lavelle
The effectiveness of many vaccines licensed for clinical use relates to the induction of neutralising antibodies, facilitated by the inclusion of vaccine adjuvants, particularly alum. However, the ability of alum to preferentially promote humoral rather than cellular, particularly Th1-type responses, is not well understood. We demonstrate that alum activates immunosuppressive mechanisms following vaccination, which limit its capacity to induce Th1 responses. One of the key cytokines limiting excessive immune responses is IL-10...
January 19, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29349609/caspase-1-mediated-pyroptosis-of-the-predominance-for-driving-cd4-formula-see-text-t-cells-death-a-nonlocal-spatial-mathematical-model
#20
Wei Wang, Tongqian Zhang
Caspase-1-mediated pyroptosis is the predominance for driving CD4[Formula: see text] T cells death. Dying infected CD4[Formula: see text] T cells can release inflammatory signals which attract more uninfected CD4[Formula: see text] T cells to die. This paper is devoted to developing a diffusive mathematical model which can make useful contributions to understanding caspase-1-mediated pyroptosis by inflammatory cytokines IL-1[Formula: see text] released from infected cells in the within-host environment. The well-posedness of solutions, basic reproduction number, threshold dynamics are investigated for spatially heterogeneous infection...
January 18, 2018: Bulletin of Mathematical Biology
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