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https://www.readbyqxmd.com/read/29150630/inhibition-of-myeloid-differentiation-primary-response-protein-88-provides-neuroprotection-in-early-brain-injury-following-experimental-subarachnoid-hemorrhage
#1
Huiying Yan, Dingding Zhang, Yongxiang Wei, Hongbin Ni, Weibang Liang, Huasheng Zhang, Shuangying Hao, Wei Jin, Kuanyu Li, Chun-Hua Hang
Accumulating of evidence suggests that activation of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) exacerbates early brain injury (EBI) following subarachnoid hemorrhage (SAH) by provoking pro-inflammatory and pro-apoptotic signaling. Myeloid differentiation primary response protein 88 (MyD88) is an endogenous adaptor protein in the toll-like receptors (TLRs) and interleukin (IL) -1β family signaling pathways and acts as a bottle neck in the NF-κB and MAPK pathways. Here, we used ST2825, a selective inhibitor of MyD88, to clarify whether inhibiting MyD88 could provide neuroprotection in EBI following SAH...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29150602/tlr7-mediated-viral-recognition-results-in-focal-type-i-interferon-secretion-by-dendritic-cells
#2
Shin-Ichiroh Saitoh, Fumiko Abe, Atsuo Kanno, Natsuko Tanimura, Yoshiko Mori Saitoh, Ryutaro Fukui, Takuma Shibata, Katsuaki Sato, Takeshi Ichinohe, Mayumi Hayashi, Kazuishi Kubota, Hiroko Kozuka-Hata, Masaaki Oyama, Yorifumi Kikko, Toshiaki Katada, Kenji Kontani, Kensuke Miyake
Plasmacytoid dendritic cells (pDC) sense viral RNA through toll-like receptor 7 (TLR7), form self-adhesive pDC-pDC clusters, and produce type I interferons. This cell adhesion enhances type I interferon production, but little is known about the underlying mechanisms. Here we show that MyD88-dependent TLR7 signaling activates CD11a/CD18 integrin to induce microtubule elongation. TLR7(+) lysosomes then become linked with these microtubules through the GTPase Arl8b and its effector SKIP/Plekhm2, resulting in perinuclear to peripheral relocalization of TLR7...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29147584/il-33-acts-to-express-schaffer-collateral-ca1-ltp-and-regulate-learning-and-memory-by-targeting-myd88
#3
Tomoyuki Nishizaki
Interleukin-33 (IL-33) is recognized to transmit a signal through a heterodimeric receptor complex ST2/interleukin-1 receptor accessory protein (IL-1RAcP) bearing activation of myeloid differentiation factor 88 (MyD88). High-frequency stimulation to the Schaffer collateral induced long-term potentiation (LTP) in the CA1 region of hippocampal slices from wild-type control mice. Schaffer collateral/CA1 LTP in IL-33-deficient mice was significantly suppressed, which was neutralized by application with IL-33. Similar suppression of the LTP was found with MyD88-deficient mice but not with ST2-deficient mice...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/29147012/piperidylmethyloxychalcone-improves-immune-mediated-acute-liver-failure-via-inhibiting-tak1-activity
#4
Sun Hong Park, Jeong-Ah Kwak, Sang-Hun Jung, Byeongwoo Ahn, Won-Jea Cho, Cheong-Yong Yun, Chang Seon Na, Bang Yeon Hwang, Jin Tae Hong, Sang-Bae Han, Youngsoo Kim
Mice deficient in the toll-like receptor (TLR) or the myeloid differentiation factor 88 (MyD88) are resistant to acute liver failure (ALF) with sudden death of hepatocytes. Chalcone derivatives from medicinal plants protect from hepatic damages including ALF, but their mechanisms remain to be clarified. Here, we focused on molecular basis of piperidylmethyloxychalcone (PMOC) in the treatment of TLR/MyD88-associated ALF. C57BL/6J mice were sensitized with D-galactosamine (GalN) and challenged with Escherichia coli lipopolysaccharide (LPS, TLR4 agonist) or oligodeoxynucleotide containing unmethylated CpG motif (CpG ODN, TLR9 agonist) for induction of ALF...
November 17, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29144391/antimicrobial-peptide-epinecidin-1-modulates-myd88-protein-levels-via-the-proteasome-degradation-pathway
#5
Bor-Chyuan Su, Jyh-Yih Chen
The cationic antimicrobial peptide epinecidin-1 was identified from Epinephelus coioides and possesses multiple biological functions, including antibacterial, antifungal, anti-tumor, and immunomodulatory effects. In addition, epinecidin-1 suppresses lipopolysaccharide (LPS)-induced inflammation by neutralizing LPS and ameliorating LPS/Toll-like receptor (TLR)-4 internalization. However, it is unclear whether the actions of epinecidin-1 depend on the regulation of TLR adaptor protein MyD88 or endogenous TLR signaling antagonists, which include A20, interleukin-1 receptor associated kinase (IRAK)-M, and suppressor of cytokine signaling (SOCS)-1...
November 16, 2017: Marine Drugs
https://www.readbyqxmd.com/read/29142761/aeromonas-hydrophila-utilizes-tlr4-topology-for-synchronous-activation-of-myd88-and-trif-to-orchestrate-anti-inflammatory-responses-in-zebrafish
#6
Nidhi Srivastava, Asha Shelly, Manmohan Kumar, Archana Pant, Bhabatosh Das, Tanmay Majumdar, Shibnath Mazumder
Toll-like receptor 4 (TLR4) plays a critical role in host immunity against Gram-negative bacteria. It transduces signals through two distinct TIR-domain-containing adaptors, MyD88 and TRIF, which function at the plasma membrane and endosomes, respectively. Using zebrafish Aeromonas hydrophila infection model, we demonstrate that synchronization of MyD88 and TRIF dependent pathways is critical for determining the fate of infection. Zebrafish were infected with A. hydrophila, and bacterial recovery studies suggested its effective persistence inside the host...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/29133782/mtor-intersects-antibody-inducing-signals-from-taci-in-marginal-zone-b-cells
#7
Jordi Sintes, Maurizio Gentile, Shuling Zhang, Yolanda Garcia-Carmona, Giuliana Magri, Linda Cassis, Daniel Segura-Garzón, Alessandra Ciociola, Emilie K Grasset, Sabrina Bascones, Laura Comerma, Marc Pybus, David Lligé, Irene Puga, Cindy Gutzeit, Bing He, Wendy DuBois, Marta Crespo, Julio Pascual, Anna Mensa, Juan Ignacio Aróstegui, Manel Juan, Jordi Yagüe, Sergi Serrano, Josep Lloreta, Eric Meffre, Michael Hahne, Charlotte Cunningham-Rundles, Beverly A Mock, Andrea Cerutti
Mechanistic target of rapamycin (mTOR) enhances immunity in addition to orchestrating metabolism. Here we show that mTOR coordinates immunometabolic reconfiguration of marginal zone (MZ) B cells, a pre-activated lymphocyte subset that mounts antibody responses to T-cell-independent antigens through a Toll-like receptor (TLR)-amplified pathway involving transmembrane activator and CAML interactor (TACI). This receptor interacts with mTOR via the TLR adapter MyD88. The resulting mTOR activation instigates MZ B-cell proliferation, immunoglobulin G (IgG) class switching, and plasmablast differentiation through a rapamycin-sensitive pathway that integrates metabolic and antibody-inducing transcription programs, including NF-κB...
November 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29131267/interleukin-33-promotes-the-inflammatory-reaction-in-chronic-rhinosinusitis-with-nasal-polyps-by-nf-%C3%AE%C2%BAb-signaling-pathway
#8
L Zhang, L-L Jiang, Z-W Cao
OBJECTIVE: Interleukin (IL)-33 promotes T helper (Th2) immune response and may be involved in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). Using murine and human specimens, we evaluated the role of IL-33 in CRSwNP. MATERIALS AND METHODS: To establish CRSwNP, Balb/c mice were sensitized with house dust mite, followed up by intranasal exposure to Staphylococcus aureus to stimulate the inflammatory response of nasal mucosa. The hematoxylin-eosin staining and total serum IgE were used to the successful construction of CRSwNP model...
October 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29128927/toll-like-receptors-participate-in-naegleria-fowleri-recognition
#9
Moisés Martínez-Castillo, Leopoldo Santos-Argumedo, José Manuel Galván-Moroyoqui, Jesús Serrano-Luna, Mineko Shibayama
Naegleria fowleri is a protozoan that invades the central nervous system and causes primary amoebic meningoencephalitis. It has been reported that N. fowleri induces an important inflammatory response during the infection. In the present study, we evaluated the roles of Toll-like receptors in the recognition of N. fowleri trophozoites by human mucoepithelial cells, analyzing the expression and production of innate immune response mediators. After amoebic interactions with NCI-H292 cells, the expression and production levels of IL-8, TNF-α, IL-1β, and human beta defensin-2 were evaluated by RT-PCR, ELISA, immunofluorescence, and dot blot assays, respectively...
November 11, 2017: Parasitology Research
https://www.readbyqxmd.com/read/29128406/recognition-of-candida-albicans-by-gingival-fibroblasts-the-role-of-tlr2-tlr4-cd14-and-myd88
#10
Claudia Ramos Pinheiro, Ana Lúcia Coelho, Carine Ervolino de Oliveira, Thaís Helena Gasparoto, Gustavo Pompermaier Garlet, João Santana Silva, Carlos Ferreira Santos, Karen Angélica Cavassani, Cory M Hogaboam, Ana Paula Campanelli
Recent evidence indicates that nonprofessional immune cells such as epithelial cells, endothelial cells, and fibroblasts also contribute to innate immunity via secretion of cytokines. Fibroblasts are the principal type of cell found in the periodontal connective tissues and they are involved in the immune response during periodontal disease. The role of fibroblasts in the recognition of pathogens via Toll-like receptors (TLRs) has been established; however, few studies have been conducted concerning the involvement of innate immune receptors in the recognition of Candida albicans by gingival fibroblast...
November 8, 2017: Cytokine
https://www.readbyqxmd.com/read/29127662/jnj7777120-ameliorates-inflammatory-and-oxidative-manifestations-in-a-murine-model-of-contact-hypersensitivity-via-modulation-of-tlr-and-nrf2-signaling
#11
Ahmed F Mohamed, Mohammed F El-Yamany, Fatma A El-Batrawy, Mohamed T Abdel-Aziz
JNJ7777120, a histamine H4 receptor antagonist, was shown to be effective in different experimental settings of allergic inflammation, including contact hypersensitivity. Toll-like receptors (TLRs) are thought to function as a link between innate and adaptive immune responses to various haptens. Here, we studied the suppression of TLR signaling as a possible mechanism by which JNJ7777120 exerts its anti-inflammatory effects against the chemical hapten, fluorescein isothiocyanate (FITC). The potential anti-oxidant effect of JNJ7777120 in this model was also examined...
November 10, 2017: Inflammation
https://www.readbyqxmd.com/read/29123520/dexd-h-box-helicase-36-signaling-via-myeloid-differentiation-primary-response-gene-88-contributes-to-nf-%C3%AE%C2%BAb-activation-to-type-2-porcine-reproductive-and-respiratory-syndrome-virus-infection
#12
Huiyuan Jing, Yanrong Zhou, Liurong Fang, Zhen Ding, Dang Wang, Wenting Ke, Huanchun Chen, Shaobo Xiao
DExD/H-box helicase 36 (DHX36) is known to be an ATP-dependent RNA helicase that unwinds the guanine-quadruplexes DNA or RNA, but emerging data suggest that it also functions as pattern recognition receptor in innate immunity. Porcine reproductive and respiratory syndrome virus (PRRSV) is an Arterivirus that has been devastating the swine industry worldwide. Interstitial pneumonia is considered to be one of the most obvious clinical signs of PRRSV infection, suggesting that the inflammatory response plays an important role in PRRSV pathogenesis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29122821/metagenomic-deep-sequencing-of-aqueous-fluid-detects-intraocular-lymphomas
#13
John Gonzales, Thuy Doan, Jessica G Shantha, Michele Bloomer, Michael R Wilson, Joseph L DeRisi, Nisha Acharya
INTRODUCTION: Currently, the detection of pathogens or mutations associated with intraocular lymphomas heavily relies on prespecified, directed PCRs. With metagenomic deep sequencing (MDS), an unbiased high-throughput sequencing approach, all pathogens as well as all mutations present in the host's genome can be detected in the same small amount of ocular fluid. METHODS: In this cross-sectional case series, aqueous fluid samples from two patients were submitted to MDS to identify pathogens as well as common and rare cancer mutations...
November 9, 2017: British Journal of Ophthalmology
https://www.readbyqxmd.com/read/29120744/staphylococcus-aureus-virulent-psm%C3%AE-peptides-induce-keratinocyte-alarmin-release-to-orchestrate-il-17-dependent-skin-inflammation
#14
Seitaro Nakagawa, Masanori Matsumoto, Yuki Katayama, Rena Oguma, Seiichiro Wakabayashi, Tyler Nygaard, Shinobu Saijo, Naohiro Inohara, Michael Otto, Hiroyuki Matsue, Gabriel Núñez, Yuumi Nakamura
Staphylococcus aureus commonly colonizes the epidermis, but the mechanisms by which the host senses virulent, but not commensal, S. aureus to trigger inflammation remain unclear. Using a murine epicutaneous infection model, we found that S. aureus-expressed phenol-soluble modulin (PSM)α, a group of secreted virulence peptides, is required to trigger cutaneous inflammation. PSMα induces the release of keratinocyte IL-1α and IL-36α, and signaling via IL-1R and IL-36R was required for induction of the pro-inflammatory cytokine IL-17...
November 8, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/29120743/staphylococcus-aureus-epicutaneous-exposure-drives-skin-inflammation-via-il-36-mediated-t-cell-responses
#15
Haiyun Liu, Nathan K Archer, Carly A Dillen, Yu Wang, Alyssa G Ashbaugh, Roger V Ortines, Tracy Kao, Steven K Lee, Shuting S Cai, Robert J Miller, Mark C Marchitto, Emily Zhang, Daniel P Riggins, Roger D Plaut, Scott Stibitz, Raif S Geha, Lloyd S Miller
Staphylococcus aureus colonization contributes to skin inflammation in diseases such as atopic dermatitis, but the signaling pathways involved are unclear. Herein, epicutaneous S. aureus exposure to mouse skin promoted MyD88-dependent skin inflammation initiated by IL-36, but not IL-1α/β, IL-18, or IL-33. By contrast, an intradermal S. aureus challenge promoted MyD88-dependent host defense initiated by IL-1β rather than IL-36, suggesting that different IL-1 cytokines trigger MyD88 signaling depending on the anatomical depth of S...
November 8, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/29119662/toxoplasma-gondii-infection-shifts-dendritic-cells-into-an-amoeboid-rapid-migration-mode-encompassing-podosome-dissolution-secretion-of-timp-1-and-reduced-proteolysis-of-extracellular-matrix
#16
Einar B Ólafsson, Manuel Varas-Godoy, Antonio Barragan
Dendritic cells (DCs) infected by Toxoplasma gondii rapidly acquire a hypermigratory phenotype that promotes systemic parasite dissemination by a 'Trojan horse' mechanism in mice. Recent paradigms of leukocyte migration have identified the amoeboid migration mode of DCs as particularly suited for rapid locomotion in extracellular matrix and tissues. Here, we have developed a microscopy-based high-throughput approach to assess motility and matrix degradation by Toxoplasma-challenged murine and human DCs. DCs challenged with T...
November 8, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/29118245/mer-receptor-tyrosine-kinase-signaling-prevents-self-ligand-sensing-and-aberrant-selection-in-germinal-centers
#17
Stephanie L Schell, Chetna Soni, Melinda J Fasnacht, Phillip P Domeier, Timothy K Cooper, Ziaur S M Rahman
Mer tyrosine kinase (Mer) signaling maintains immune tolerance by clearing apoptotic cells (ACs) and inducing immunoregulatory signals. We previously showed that Mer-deficient mice (Mer(-/-)) have increased germinal center (GC) responses, T cell activation, and AC accumulation within GCs. Accumulated ACs in GCs can undergo necrosis and release self-ligands, which may influence the outcome of a GC response and selection. In this study, we generated Mer(-/-) mice with a global MyD88, TLR7, or TLR9 deficiency and cell type-specific MyD88 deficiency to study the functional correlation between Mer and TLRs in the development of GC responses and autoimmunity...
November 8, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29115619/administration-of-chlorogenic-acid-alleviates-spinal-cord-injury-via-tlr4-nf%C3%A2-%C3%AE%C2%BAb-and-p38-signaling-pathway-anti%C3%A2-inflammatory-activity
#18
Dayong Chen, Dan Pan, Shaolong Tang, Zhihong Tan, Yanan Zhang, Yunfeng Fu, Guohua Lü, Qinghua Huang
Chlorogenic acid, as a secondary metabolite of plants, exhibits a variety of effects including free radical scavenging, antiseptic, anti‑inflammatory and anti‑viral, in addition to its ability to reduce blood glucose, protect the liver and act as an anti‑hyperlipidemic agent and cholagogue. The present study demonstrated that administration of chlorogenic acid alleviated spinal cord injury (SCI) via anti‑inflammatory activity mediated by nuclear factor (NF)‑κB and p38 signaling pathways. Wistar rats were used to structure a SCI model rat to explore the effects of administration of chlorogenic acid on SCI...
November 6, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29115481/sparstolonin-b-prevents-lumbar-intervertebral-disc-degeneration-through-toll-like-receptor-4-nadph-oxidase-activation-and-the-protein-kinase-b-signaling-pathway
#19
Jianhua Ge, Long Chen, Yunkang Yang, Xiaobo Lu, Zhou Xiang
Intervertebral disc degeneration (IVDD) is the most common pathogeny of lumbago. It is the pathological basis for a series of spinal degenerative diseases. For a long time, the diagnosis and treatment of lumbago have rendered difficult, since the pathogeny has not been identified. Therefore, the present study aimed to investigate the protective effect of Sparstolonin B in preventing lumbar intervertebral disc degeneration, and explored its potential mechanism in rats. Firstly, Sparstolonin B effectively reduced the histological score of disc degeneration and increased endplate porosity of L2 superior endplates in a lumbar IVDD rat model...
November 6, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29115472/anti-inflammatory-activity-of-resveratrol-prevents-inflammation-by-inhibiting-nf%C3%A2-%C3%AE%C2%BAb-in-animal-models-of-acute-pharyngitis
#20
Zhong-Xin Zhou, Shao-Feng Mou, Xiao-Qin Chen, Li-Li Gong, Wen-Sheng Ge
Recent studies have demonstrated that resveratrol can reduce blood sugar, improve insulin resistance, regulate abnormalities in lipid metabolism, and lower the secretion and expression of inflammatory factors. The present study investigated the anti‑inflammatory effects of resveratrol in animal models of acute pharyngitis, and its possible mechanisms. Commercial ELISA kits were used to measure tumor necrosis factor‑α, interleukin (IL)‑6, macrophage inflammatory protein‑2, cyclooxygenase‑2 levels and caspase‑3/9 activity...
November 2, 2017: Molecular Medicine Reports
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