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https://www.readbyqxmd.com/read/29475090/elevated-intragraft-expression-of-innate-immunity-and-cell-death-related-markers-is-a-risk-factor-for-adverse-graft-outcome
#1
Jianxin Yang, Malou L H Snijders, Geert W Haasnoot, Cees van Kooten, Marko Mallat, Johan W de Fijter, Marian C Clahsen-van Groningen, Frans H J Claas, Michael Eikmans
BACKGROUND: Molecules of the innate immune response are increasingly recognized as important mediators in allograft injury during and after kidney transplantation. We therefore aimed to establish the relationship between the expression of these genes at implantation, during an acute rejection (AR) and on graft outcome. METHODS: A total of 19 genes, including Toll like receptors (TLRs), complement components and regulators, and apoptosis-related genes were analyzed at the mRNA level by qPCR in 123 biopsies with acute rejection and paired pre-transplantation tissue (n = 75)...
February 20, 2018: Transplant Immunology
https://www.readbyqxmd.com/read/29474381/comprehensive-analysis-of-clinical-burkholderia-pseudomallei-isolates-demonstrates-conservation-of-unique-lipid-a-structure-and-tlr4-dependent-innate-immune-activation
#2
Sineenart Sengyee, Sung Hwan Yoon, Suporn Paksanont, Thatcha Yimthin, Vanaporn Wuthiekanun, Direk Limmathurotsakul, T Eoin West, Robert K Ernst, Narisara Chantratita
Burkholderia pseudomallei is an environmental bacterium that causes melioidosis, a major community-acquired infection in tropical regions. Melioidosis presents with a range of clinical symptoms, is often characterized by a robust inflammatory response, may relapse after treatment, and results in high mortality rates. Lipopolysaccharide (LPS) of B. pseudomallei is a potent immunostimulatory molecule comprised of lipid A, core, and O-polysaccharide (OPS) components. Four B. pseudomallei LPS types have been described based on SDS-PAGE patterns that represent the difference of OPS-type A, type B, type B2 and rough LPS...
February 23, 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29472602/hpv-transformed-cells-exhibit-altered-hmgb1-tlr4-myd88-sarm1-signaling-axis
#3
Mirian Galliote Morale, Walason da Silva Abjaude, Aline Montenegro Silva, Luisa Lina Villa, Enrique Boccardo
Cervical cancer is one of the leading causes of cancer death in women worldwide. Persistent infection with high-risk human papillomavirus (HPV) types is the main risk factor for the development of cervical cancer precursor lesions. HPV persistence and tumor development is usually characterized by innate immune system evasion. Alterations in Toll-like receptors (TLR) expression and activation may be important for the control of HPV infections and could play a role in the progression of lesions and tumors. In the present study, we analyzed the mRNA expression of 84 genes involved in TLR signaling pathways...
February 22, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29472126/development-of-benzoxazole-deoxybenzoin-oxime-and-acyloxylamine-derivatives-targeting-innate-immune-sensors-and-xanthine-oxidase-for-treatment-of-gout
#4
Jun Huang, Zehao Zhou, Mengze Zhou, Mingxing Miao, Huanqiu Li, Qinghua Hu
Both the inhibition of inflammatory flares and the treatment of hyperuricemia itself are included in the management of gout. Extending our efforts to development of gout therapy, two series of benzoxazole deoxybenzoin oxime derivatives as inhibitors of innate immune sensors and xanthine oxidase (XOD) were discovered in improving hyperuricemia and acute gouty arthritis. In vitro studies revealed that most compounds not only suppressed XOD activity, but blocked activations of NOD-like receptor (NLRP3) inflammasome and Toll-like receptor 4 (TLR4) signaling pathway...
February 12, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29472103/p204-is-required-for-canonical-lipopolysaccharide-induced-tlr4-signaling-in-mice
#5
Young-Su Yi, Jinlong Jian, Elena Gonzalez-Gugel, Yong-Xiang Shi, Qingyun Tian, Wenyu Fu, Aubryanna Hettinghouse, Wenhao Song, Ronghan Liu, Michun He, Huabing Qi, Jing Yang, Xiaolan Du, GuoZhi Xiao, Lin Chen, Chuan-Ju Liu
p204, a murine member of an interferon-inducible p200 family, was reported to recognize intracellular viral and bacterial DNAs, however, its role in the innate immunity in vivo remains unknown due to the lack of p204-deficient animal models. In this study we first generated the p204-/- mice. Unexpectedly, p204 deficiency led to significant defect in extracellular LPS signaling in macrophages, as demonstrated by dramatic reductions of LPS-mediated IFN-β and pro-inflammatory cytokines. The serum levels of IFN-β and pro-inflammatory cytokines were also significantly reduced in p204-/- mice following LPS challenge...
February 16, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29471085/houttuynia-cordata-polysaccharides-ameliorate-pneumonia-severity-and-intestinal-injury-in-mice-with-influenza-virus-infection
#6
Haiyan Zhu, Xiaoxiao Lu, Lijun Ling, Hong Li, Yingye Ou, Xunlong Shi, Yan Lu, Yunyi Zhang, Daofeng Chen
ETHNOPHARMACOLOGICAL RELEVANCE: Hottuynia cordata is an important traditional Chinese medicine for the treatment of respiratory diseases including bacterial and viral infections. Polysaccharides isolated from Houttuynia cordata (HCP), as its main ingredients, have been demonstrated to ameliorate the LPS-induced acute lung injury in mice. The study aimed to determine the protective effects of HCP on multiple organ injury in influenza A virus (IAV) H1N1 infected mice and its primary mechanisms in anti-inflammation and immune regulation...
February 19, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29471030/neuroprotective-effects-of-fecal-microbiota-transplantation-on-mptp-induced-parkinson-s-disease-mice-gut-microbiota-glial-reaction-and-tlr4-tnf-%C3%AE-signaling-pathway
#7
Meng-Fei Sun, Ying-Li Zhu, Zhi-Lan Zhou, Xue-Bing Jia, Yi-Da Xu, Qin Yang, Chun Cui, Yan-Qin Shen
Parkinson's disease (PD) patients display alterations in gut microbiota composition. However, mechanism between gut microbial dysbiosis and pathogenesis of PD remains unexplored, and no recognized therapies are available to halt or slow progression of PD. Here we identified that gut microbiota from PD mice induced motor impairment and striatal neurotransmitter decrease on normal mice. Sequencing of 16S rRNA revealed that phylum Firmicutes and order Clostridiales decreased, while phylum Proteobacteria, order Turicibacterales and Enterobacteriales increased in fecal samples of PD mice, along with increased fecal short-chain fatty acids (SCFAs)...
February 19, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29470660/the-effect-of-inhalant-organic-dust-on-bone-health
#8
REVIEW
Joseph M Carrington, Jill A Poole
PURPOSE OF REVIEW: Agriculture remains a major economic sector globally, and workers experience high rates of chronic inflammatory lung and musculoskeletal diseases. Whereas obstructive pulmonary diseases are known risk factors for bone loss, the underlying relationship between lung inflammation and bone health is not well known. RECENT FINDINGS: An agriculture organic dust extract inhalation animal model has recently linked lung injury-induced inflammation to systemic bone loss...
February 22, 2018: Current Allergy and Asthma Reports
https://www.readbyqxmd.com/read/29468499/resveratrol-improves-neuroimmune-dysregulation-through-the-inhibition-of-neuronal-toll-like-receptors-and-cox-2-signaling-in-btbr-t-itpr3-tf-j-mice
#9
Sheikh F Ahmad, Mushtaq A Ansari, Ahmed Nadeem, Mohammad Z Alzahrani, Saleh A Bakheet, Sabry M Attia
Autism is a neurodevelopmental disorder characterized by deficits in qualitative impairments in communication, repetitive and social interaction, restricted, and stereotyped patterns of behavior. Resveratrol has been extensively studied pharmacologically and biologically and has anti-inflammatory, antioxidant, and neuroprotective effects on neuronal damage in neurodegenerative disorders. The BTBR T+ Itpr3tf /J (BTBR) autistic mouse model has been explored for treatment of autism, which shows low reciprocal social interactions, impaired juvenile play, and decreased social approach...
February 21, 2018: Neuromolecular Medicine
https://www.readbyqxmd.com/read/29467931/toll-like-receptor-2-induces-adenosine-receptor-a2a-and-promotes-human-squamous-carcinoma-cell-growth-via-extracellular-signal-regulated-kinases-%C3%A2
#10
Chithra Devi Palani, Lalitha Ramanathapuram, Aroonwan Lam-Ubol, Zoya B Kurago
Patient treatment for oral squamous cell carcinoma (OSCC) not associated with Human papillomavirus remains problematic. OSCC microenvironment is typically inflamed and colonized by microorganisms, providing ligands for toll-like receptors (TLR). In immune cells TLR2 and TLR4 activate NF-kB and extracellular signal regulated kinase (ERK)1/2 pathways, leading to upregulation of inhibitory adenosine receptors A2a and A2b, and reduction in stimulatory A1 and A3. How TLR and adenosine receptors function in SCC cells is not understood...
January 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29466778/new-md2-inhibitors-derived-from-curcumin-with-improved-anti-inflammatory-activity
#11
Yali Zhang, Zhiguo Liu, Jianzhang Wu, Bin Bai, Hongjin Chen, Zhongxiang Xiao, Lingfeng Chen, Yunjie Zhao, Hazel Lum, Yi Wang, Hong Zhang, Guang Liang
An overactive Toll-like receptor (TLR) signaling complex is a significant pathogenic factor of acute and chronic inflammatory diseases. The natural product curcumin is reported to inhibit the TLR4 co-receptor, MD2 (myeloid differentiation protein 2), but its low in vivo bioavailability limits its therapeutic potential. We developed new curcumin analogs (MACs) with removal of the β-diketone moiety and substituted residues in benzene rings, and identify these as potential MD2 inhibitors with improved inhibition potency and stability over that of curcumin...
February 15, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29466671/lipopolysaccharide-stimulates-bk-channel-activity-in-bladder-umbrella-cells
#12
Ming Lu, Jian-Ri Li, Lery Alvarez-Lugo, Yan Li, Shan Yu, Xuanhao Li, Benkang Shi, Toby C Chai
Bladder urothelium plays an active role in response to bacterial infection. There is little known about the electrophysiological activity in urothelial cells in this process. We used a non-enzymatic method to isolate bladder urothelial tissue and to patch clamp umbrella cells in situ. A 200pS conductance potassium (K+ ) channel was detected from female C57BL6 mice. Of 58 total patches, 17.2% patches displayed the 200pS K+ conductance channel. This K+ conductance channel showed Ca2+ sensitivity and voltage dependence...
February 21, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29463677/an-unexpected-link-between-fatty-acid-synthase-and-cholesterol-synthesis-in-proinflammatory-macrophage-activation
#13
Richard G Carroll, Zbigniew Zaslona, Silvia Galván-Peña, Emma L Koppe, Daniel C Sévin, Stefano Angiari, Martha Triantafilou, Kathy Triantafilou, Louise K Modis, Luke O'Neill
Different immune activation states require distinct metabolic features and activities in immune cells. For instance, inhibition of fatty acid synthase (FASN), which catalyzes the synthesis of long-chain fatty acids, prevents the proinflammatory response in macrophages; however, the precise role of this enzyme in this response remains poorly defined. Consistent with previous studies, we found here that FASN is essential for lipopolysaccharide-induced, Toll-like receptor (TLR)-mediated macrophage activation. Interestingly, only agents that block FASN upstream of acetoacetyl-CoA synthesis, including the well-characterized FASN inhibitor C75, inhibited TLR4 signaling, while those acting downstream had no effect...
February 20, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29463000/awrk6-a-synthetic-cationic-peptide-derived-from-antimicrobial-peptide-dybowskin-2cdya-inhibits-lipopolysaccharide-induced-inflammatory-response
#14
Qiuyu Wang, Lili Jin, Huan Wang, Sijia Tai, Hongsheng Liu, Dianbao Zhang
Lipopolysaccharides (LPS) are major outer membrane components of Gram-negative bacteria and produce strong inflammatory responses in animals. Most antibiotics have shown little clinical anti-endotoxin activity while some antimicrobial peptides have proved to be effective in blocking LPS. Here, the anti-LPS activity of the synthetic peptide AWRK6, which is derived from antimicrobial peptide dybowskin-2CDYa, has been investigated in vitro and in vivo. The positively charged α-helical AWRK6 was found to be effective in blocking the binding of LBP (LPS binding protein) with LPS in vitro using ELISA...
February 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29462590/lipid-bilayer-stress-in-obesity-linked-inflammatory-and-metabolic-disorders
#15
REVIEW
Marco A Gianfrancesco, Nicolas Paquot, Jacques Piette, Sylvie Legrand-Poels
The maintenance of the characteristic lipid compositions and physicochemical properties of biological membranes is essential for their proper function. Mechanisms allowing to sense and restore membrane homeostasis have been identified in prokaryotes for a long time and more recently in eukaryotes. A membrane remodeling can result from aberrant metabolism as seen in obesity. In this review, we describe how such lipid bilayer stress can account for the modulation of membrane proteins involved in the pathogenesis of obesity-linked inflammatory and metabolic disorders...
February 17, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29462003/toll-like-receptor-4-signaling-licenses-the-cytosolic-transport-of-lipopolysaccharide-from-bacterial-outer-membrane-vesicles
#16
Lan Gu, Ran Meng, Yiting Tang, Kai Zhao, Fang Liang, Rui Zhang, Qianqian Xue, Fangping Chen, Xianzhong Xiao, Huadong Wang, Haichao Wang, Timothy R Billiar, Ben Lu
Outer membrane vesicles (OMVs), released by variety of bacteria, are membrane-enclosed entities enriched in microbial components, toxins and virulent factors. OMVs could deliver lipopolysaccharide (LPS) into the cytosol of host cells and subsequently activate caspase-11, which critically orchestrates immune responses and mediates septic shock. Though it is known that caspase-11 is activated by intracellular LPS, how OMVs deliver LPS into the cytosol remains largely unknown. Here we show that the activation of toll like receptor 4 (TLR4), a LPS receptor on the cytoplasmic membrane, licenses macrophages to transport LPS from OMVs into the cytosol through TIR domain-containing adaptor-inducing interferon-β (TRIF)...
February 16, 2018: Shock
https://www.readbyqxmd.com/read/29459437/lps-targets-host-guanylate-binding-proteins-to-the-bacterial-outer-membrane-for-non-canonical-inflammasome-activation
#17
José Carlos Santos, Mathias S Dick, Brice Lagrange, Daniel Degrandi, Klaus Pfeffer, Masahiro Yamamoto, Etienne Meunier, Pawel Pelczar, Thomas Henry, Petr Broz
Pathogenic and commensal Gram-negative bacteria produce and release outer membrane vesicles (OMVs), which present several surface antigens and play an important role for bacterial pathogenesis. OMVs also modulate the host immune system, which makes them attractive as vaccine candidates. At the cellular level, OMVs are internalized by macrophages and deliver lipopolysaccharide (LPS) into the host cytosol, thus activating the caspase-11 non-canonical inflammasome. Here, we show that OMV-induced inflammasome activation requires TLR4-TRIF signaling, the production of type I interferons, and the action of guanylate-binding proteins (GBPs), both in macrophages and in vivo Mechanistically, we find that isoprenylated GBPs associate with the surface of OMVs or with transfected LPS, indicating that the key factor that determines GBP recruitment to the Gram-negative bacterial outer membranes is LPS itself...
February 19, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29458199/alpha-synuclein-oligomers-impair-memory-through-glial-cell-activation-and-via-toll-like-receptor-2
#18
Pietro La Vitola, Claudia Balducci, Milica Cerovic, Giulia Santamaria, Edoardo Brandi, Federica Grandi, Laura Caldinelli, Laura Colombo, Maria Grazia Morgese, Luigia Trabace, Loredano Pollegioni, Diego Albani, Gianluigi Forloni
Alpha-synuclein oligomers (α-synOs) are emerging as crucial factors in the pathogenesis of synucleinopathies. Although the connection between neuroinflammation and α-syn still remains elusive, increasing evidence suggests that extracellular moieties activate glial cells leading to neuronal damage. Using an acute mouse model, we explored whether α-synOs induce memory impairment in association to neuroinflammation, addressing Toll-like receptors 2 and 4 (TLR2 and TLR4) involvement. We found that α-synOs abolished mouse memory establishment in association to hippocampal glial activation...
February 16, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29456541/ifn-%C3%AF-mediated-control-of-bovine-major-histocompatibility-complex-class-i-expression-and-function-via-the-regulation-of-bta-mir-148b-152-in-bovine-endometrial-epithelial-cells
#19
Haichong Wu, Kangfeng Jiang, Shuai Guo, Jing Yang, Gan Zhao, Changwei Qiu, Ganzhen Deng
IFN-τ, a type I interferon produced by the trophoblasts of ruminants, has various important immune functions, including effects on the expression of major histocompatibility complex (MHC) class I (MHC-I). A previous study has reported that IFN-τ promotes the expression of MHC-I molecules on endometrial cells. However, the immunological mechanisms by which IFN-τ regulates MHC-I molecules remain unknown. Here, we investigated which microRNA (miRNAs) may be involved in the regulation of MHC-I molecule expression and function in bovine endometrial epithelial cells (bEECs)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29456409/recombinant-expressed-vasoactive-intestinal-peptide-analogue-ameliorates-tnbs-induced-colitis-in-rats
#20
Chun-Lan Xu, Yu Guo, Lei Qiao, Li Ma, Yi-Yi Cheng
AIM: To investigate the modulatory effect of recombinant-expressed vasoactive intestinal peptide (VIP) analogue (rVIPa) on trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. METHODS: Forty-eight rats were randomized into six groups: normal control group (Control), model control group (TNBS), ethanol treatment group (ETOH), and VIP treatment groups with different dosage (rVIPa1nmol , rVIPa2nmol , rVIPa4nmol ). Diarrhea and bloody stool were observed. Colonic damage was evaluated histologically...
February 14, 2018: World Journal of Gastroenterology: WJG
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