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https://www.readbyqxmd.com/read/29908959/low-back-pain-and-disc-degeneration-are-decreased-following-chronic-toll-like-receptor-4-inhibition-in-a-mouse-model
#1
Emerson Krock, Magali Millecamps, J Brooke Currie, Laura S Stone, Lisbet Haglund
OBJECTIVE: Intervertebral disc degeneration is a leading cause of chronic low back pain but current treatment is limited. Toll-like receptors (TLR) on disc cells are activated by endogenous extracellular matrix fragments and modulate degeneration in vitro. This study investigated whether inhibiting TLR4 slows disc degeneration and reduces behavioral signs of LBP in vivo. DESIGN: 7-9-month old wild-type and SPARC-null (a model of disc degeneration and LBP) male mice were treated with TAK-242 (TLR4 inhibitor) once, and following a 10-day washout, mice were treated 3 times/week for 8 weeks...
June 14, 2018: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/29907924/heat-acclimation-increases-inflammatory-and-apoptotic-responses-to-subsequent-lps-challenge-in-c2c12-myotubes
#2
Meghan G Patton, Trevor L Gillum, Mandy C Szymanski, Lacey M Gould, Claire J Lauterbach, Roger A Vaughan, Matthew R Kuennen
This work investigated the ability of a 6-day heat acclimation protocol to impart heat acclimation-mediated cross-tolerance (HACT) in C2C12 myotubes, as indicated by changes in inflammatory and apoptotic responses to subsequent lipopolysaccharide (LPS) challenge. Myotubes were incubated at 40 °C for 2 h/day over 6 days (HA) or maintained for 6 days at 37 °C (C). Following 24 h recovery, myotubes from each group received either no stimulation or 500 ng/ml LPS for 2 h (HA + LPS and C + LPS, respectively)...
June 16, 2018: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/29907882/relevance-of-placental-type-i-interferon-beta-regulation-for-pregnancy-success
#3
Ja-Young Kwon, Paulomi Aldo, Yuan You, Jiahui Ding, Karen Racicot, Xiaoyan Dong, John Murphy, Guy Glukshtad, Michelle Silasi, Jian Peng, Li Wen, Vikki M Abrahams, Roberto Romero, Gil Mor
Pregnancy is a unique immunologic and microbial condition that requires an adequate level of awareness to provide a fast and protective response against pathogens as well as to maintain a state of tolerance to paternal antigens. Dysregulation of inflammatory pathways in the placenta triggered by pathogens is one of the main factors responsible for pregnancy complications. Type I IFNs are key molecules modulating immune responses at the level of the placenta and are crucial for protection of the pregnancy via their antiviral and immune modulatory properties...
June 15, 2018: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29907783/protective-effect-of-hydroxysafflor-yellow-a-against-acute-kidney-injury-via-the-tlr4-nf-%C3%AE%C2%BAb-signaling-pathway
#4
Juan Bai, Jinyi Zhao, Dongxiao Cui, Fan Wang, Ying Song, Lianghua Cheng, Kai Gao, Jin Wang, Long Li, Shujun Li, Yanyan Jia, Aidong Wen
This study aimed to evaluate the protective effect of hydroxysafflor yellow A (HSYA) on ischemia/reperfusion (I/R)-induced acute kidney injury via the TLR4/NF-κB pathway, both in vitro and in vivo. Rats were subjected to removal of the right kidney and I/R injury to the left kidney. Rats subjected to renal I/R injury were treated with HSYA at 0.5 h prior to I/R injury. Renal function, histopathological analysis, and cells apoptosis were measured in vivo. In vitro, proximal renal tubular cells (HK-2) were subjected to hypoxia/reoxygenation (H/R)...
June 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29907431/the-hyaluronic-acid-rich-node-and-duct-system-is-a-structure-organized-for-innate-immunity-and-mediates-the-local-inflammation
#5
Beom K Choi, Sun H Hwang, Yu I Kim, Rohit Singh, Byoung S Kwon
The Hyaluronic Acid-rich Node and Duct System (HAR-NDS or NDS), Primo Vascular System (PVS) or Bonghan System (BHS), is thought to be a third circulatory system independent of the blood and lymphatic systems and a structure of connected nodes and ducts. Although it seems to be part of the immune system as it is enriched with cells of innate immunity, little is known about its immunological roles. We performed cellular profiling and secretome analysis of NDS in a steady state and under TLR2- or TLR4-mediated local inflammation, and found that the NDS is pre-dominantly enriched with the myeloid cells, selectively attracts the inflammatory macrophages and neutrophils, has a flexible structure just like the lymph node, and is structured with the fibroblastic reticular cells and reticular network...
June 12, 2018: Cytokine
https://www.readbyqxmd.com/read/29906814/magnoflorine-enhances-lps-activated-pro-inflammatory-responses-via-myd88-dependent-pathways-in-u937-macrophages
#6
Md Areeful Haque, Ibrahim Jantan, Hemavathy Harikrishnan, Siti Mariam Abdul Wahab
Magnoflorine, a major bioactive metabolite isolated from Tinospora crispa, has been reported for its diverse biochemical and pharmacological properties. However, there is little report on its underlying mechanisms of action on immune responses, particularly on macrophage activation. In this study, we aimed to investigate the effects of magnoflorine, isolated from T. crispa on the pro-inflammatory mediators generation induced by LPS and the concomitant NF- κ B, MAPKs, and PI3K-Akt signaling pathways in U937 macrophages...
June 15, 2018: Planta Medica
https://www.readbyqxmd.com/read/29906742/xanthohumol-attenuates-cisplatin-induced-nephrotoxicity-through-inhibiting-nf-%C3%AE%C2%BAb-and-activating-nrf2-signaling-pathways
#7
Fan Li, Yunyi Yao, Hui Huang, Hua Hao, Mingzhong Ying
Cisplatin is a chemotherapeutic agent that widely used in the treatment of cancer. However, cisplatin has been reported to induce nephrotoxicity by directly inducing inflammatory response and oxidative stress. In this study, we aimed to investigate the protective effects and mechanism of xanthohumol on cisplatin-induced nephrotoxicity. The model of nephrotoxicity was induced by intraperitoneal injection of cisplatin and xanthohumol was given intraperitoneally for three consecutive days. The results showed that xanthohumol significantly attenuated kidney histological changes and serum creatinine and BUN production...
June 12, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29906494/dihydronortanshinone-a-natural-product-alleviates-lps-induced-inflammatory-response-through-nf-%C3%AE%C2%BAb-mitochondrial-ros-and-mapk-pathways
#8
Xiaxia Wu, Hongwei Gao, Ying Hou, Jie Yu, Wen Sun, Ying Wang, Xiaoyan Chen, Yulin Feng, Qiong-Ming Xu, Xiuping Chen
Inflammation is considered to be the common pathophysiological basis for a series of diseases. Documented data showed the anti-inflammatory effects of Salvia miltiorrhiza Bunge (Danshen), a traditional herb. The pharmacological activities of dihydronortanshinone (DNT), a tanshinone isolated from Danshen, remain unknown. In this study, the anti-inflammatory effects and underlying mechanisms of DNT were investigated with a lipopolysaccharide (LPS)-induced RAW264.7 macrophage model. DNT significantly suppressed LPS-induced inflammatory mediators such as nitrite oxide (NO), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), inducible nitric oxide synthase (iNOS)...
June 12, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29906247/a-critical-role-for-abc-transporters-in-persistent-lung-inflammation-in-the-development-of-emphysema-after-smoke-exposure
#9
Jarrod Sonett, Monica Goldklang, Piotr Sklepkiewicz, Adam Gerber, Jordis Trischler, Tina Zelonina, Marit Westerterp, Vincent Lemaître, Yasunori Okada, Jeanine D'Armiento
Macrophage infiltration is common to both emphysema and atherosclerosis, and cigarette smoke down-regulates the macrophage cholesterol efflux transporter ATP binding cassette (ABC)A1. This decreased cholesterol efflux results in lipid-laden macrophages. We hypothesize that cigarette smoke adversely affects cholesterol transport via an ABCA1-dependent mechanism in macrophages, enhancing TLR4/myeloid differentiation primary response gene 88 (Myd88) signaling and resulting in matrix metalloproteinase (MMP) up-regulation and exacerbation of pulmonary inflammation...
June 15, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29906103/cell-based-green-fluorescent-biosensor-using-cytotoxic-pathway-for-bacterial-lipopolysaccharide-recognition
#10
Jiadi Sun, Pei Zhu, Xiumei Wang, Jian Ji, Jean de Dieu Habimana, Jingdong Shao, Hongtao Lei, Yinzhi Zhang, Xiulan Sun
Lipopolysaccharide (LPS), a characteristic component of the outer membrane of Gram-negative bacteria, can be used as an effective biomarker to detect bacterial contamination. Here, we reported a 293/hTLR4A-MD2-CD14 cell-based fluorescent biosensor to detect and identify LPS, which is carried out in a 96-well microplate with nondestructive, user-friendly and high efficiency. The promoter sequence of the critical signaling pathway gene ZC3H12A (encoding MCPIP1 protein) and Enhanced Green Fluorescence Protein (EGFP) were combined to construct a recombinant plasmid, which was transferred into 293/hTLR4A-MD2-CD14 cells through lipid-mediated, DNA-transfection way...
June 15, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29904116/neutrophil-tlr4-and-pkr-are-targets-of-breast-cancer-cell-glycosaminoglycans-and-effectors-of-glycosaminoglycan-induced-april-secretion
#11
Uilst Bat-Erdene, Eric Quan, Kelvin Chan, Brianna-Marie Lee, Wejdan Matook, Ki-Young Lee, Jesusa L Rosales
A proliferation-inducing ligand (APRIL), which induces survival and migration signals and tumor growth, is commonly observed in breast cancer tissues but is not often expressed in breast cancer cells themselves. Here, we examined whether breast cancer cells induce APRIL secretion from neutrophils, which are frequently recruited into the breast tumor microenvironment. We found that breast cancer cells do stimulate neutrophils to secrete APRIL through their glycosaminoglycans. Breast cancer cells depleted of heparan sulfate or chondroitin sulfate glycosaminoglycans lose their ability to induce APRIL secretion from neutrophils, and heparan sulfate and chondroitin sulfate can induce secretion that is comparable to that of breast cancer cell-induced secretion...
June 15, 2018: Oncogenesis
https://www.readbyqxmd.com/read/29902933/a-nanoparticle-based-approach-to-improve-the-outcome-of-cancer-active-immunotherapy-with-lipopolysaccharides
#12
Maryam A Shetab Boushehri, Mona M A Abdel-Mottaleb, Arnaud Béduneau, Yann Pellequer, Alf Lamprecht
This study sought to develop a simple nanoparticle-based approach to enhance the efficiency and tolerability of lipopolysaccharide (LPS), a potent ligand of Toll-like Receptor 4 (TLR4), for immunotherapy in cancer. Despite holding promise within this context, the strong pro-inflammatory properties of LPS also account for its low tolerability given localized and systemic side effects, which restrict the administrable dosage. Herein, we investigated the effect of LPS decoration as a surface-active molecule on a polymeric matrix upon its efficiency and tolerability...
November 2018: Drug Delivery
https://www.readbyqxmd.com/read/29902710/protective-effects-of-ginsenoside-rg1-against-lipopolysaccharide-d-galactosamine-induced-acute-liver-injury-in-mice-through-inhibiting-toll-like-receptor-4-signaling-pathway
#13
Chenqing Ning, Xiaoguang Gao, Changyuan Wang, Xiaokui Huo, Zhihao Liu, Huijun Sun, Xiaobo Yang, Pengyuan Sun, Xiaodong Ma, Qiang Meng, Kexin Liu
Acute liver injury (ALI) is a dramatic liver disease characterized by large areas of inflammation in the liver. This study aimed to investigate the protective effects of ginsenoside Rg1 (Rg1), a biologically active component in Panax ginseng, on lipopolysaccharide/d-galactosamine (LPS/D-GalN)-induced ALI in mice, and meanwhile explore the molecular mechanism in vivo and in vitro. Mice were pretreated with Rg1 for three days prior to LPS (40 μg/kg)/D-GalN (700 mg/kg) administration. The results showed that Rg1 improved the survival rate and reduced the liver to body weight ratios in mice...
June 11, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29901822/malt1-blocks-il-1%C3%AE-production-by-macrophages-in-vitro-and-limits-dextran-sodium-sulfate-induced-intestinal-inflammation-in-vivo
#14
Mahdis Monajemi, Yvonne C F Pang, Saelin Bjornson, Susan C Menzies, Nico van Rooijen, Laura M Sly
This study tested the hypothesis that Malt1 deficiency in macrophages contributes to dextran sodium sulfate (DSS)-induced intestinal inflammation in Malt1-deficient mice. In people, combined immunodeficiency caused by a homozygous mutation in the MALT1 gene is associated with increased susceptibility to bacterial infections and chronic inflammation, including severe inflammation along the gastrointestinal tract. The consequences of Malt1 deficiency have largely been attributed to its role in lymphocytes, but Malt1 is also expressed in macrophages, where it is activated downstream of TLR4 and dectin-1...
June 14, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29901170/overexpression-of-mir-140-5p-inhibits-lipopolysaccharide-induced-human-intervertebral-disc-inflammation-and-degeneration-by-downregulating-toll-like-receptor-4
#15
Qiang Zhang, Yiping Weng, Yuqing Jiang, Shujie Zhao, Dong Zhou, Nanwei Xu
Toll-like receptor 4 (TLR4) families are receptors for ligands that initiate extracellular or intracellular signaling, such as lipopolysaccharides (LPS). It has been reported that TLR4 activation resulted in the upregulation of a coordinated set of proinflammatory mediators and inhibition of matrix expression in the intervertebral disc (IVD). miR-140-5p (miR-140) is reported to participate in cellular anti-inflammatory processes and target TLR4. In the present study, we investigated the relationship between TLR4 and miR-140 in IVD degeneration...
June 12, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29901164/curcumin-inhibits-liver-cancer-by-inhibiting-damp-molecule-hsp70-and-tlr4-signaling
#16
Biqiong Ren, Shudi Luo, Xuefei Tian, Zhichao Jiang, Guoying Zou, Fei Xu, Tieqiu Yin, Yiran Huang, Junlong Liu
Curcumin has been revealed to inhibit liver cancer, however, no studies have reported that the mechanism of curcumin's action on liver cancer is related to damage-associated molecular pattern (DAMP) molecules heat shock protein 70 (HSP70) and the toll-like receptor 4 (TLR4) signaling. This study aimed to investigate whether the activation of TLR4 signaling by HSP70 could be inhibited by curcumin, thus investigating the possible mechanism of curcumin in the inhibition of liver cancer. Western blotting was used to evaluate the expression of the HSP70 and TLR4 in HepG2 cells and ELISA was used to detect the concentration of HSP70 in cell culture medium...
June 11, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29901082/liquiritin-suppresses-uvb%C3%A2-induced-skin-injury-through-prevention-of-inflammation-oxidative-stress-and-apoptosis-through-the-tlr4-myd88-nf%C3%A2-%C3%AE%C2%BAb-and-mapk-caspase-signaling-pathways
#17
Xiao-Qing Li, Li-Min Cai, Jing Liu, Yan-Li Ma, Ying-Hui Kong, He Li, Ming Jiang
Solar ultraviolet B (UVB) radiation is known to trigger inflammation, oxidative stress and apoptotic responses through various signaling pathways, which eventually lead to skin cancer. The present study investigated whether liquiritin suppresses UVB‑induced skin injury in vivo and in vitro using SKH‑1 hairless mice and HACAT cells, respectively. The animals were exposed to UVB irradiation (180 mJ/cm2) for 20 min, followed by liquiritin treatment. The findings indicated that UVB exposure resulted in the excessive release of pro‑inflammatory cytokines, including interleukin (IL)‑1β, tumor necrosis factor (TNF)‑α, IL‑18, IL‑6 and cyclooxygenase (COX)2, which were dependent on the toll‑like receptor (TLR)4/myeloid differentiation factor 88 (MyD88)/nuclear factor‑κB (NF‑κB) signaling pathway...
June 5, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29900929/whey-acidic-protein-four-disulfide-core-domain-21-regulate-sepsis-pathogenesis-in-a-mouse-model-and-a-macrophage-cell-line-via-the-stat3-toll-like-receptor-4-tlr4-signaling-pathway
#18
Zhixiang Xie, Zhuangbo Guo, Jianfeng Liu
BACKGROUND Whey acidic protein/four-disulfide core domain 21 (Wfdc21), also known as Lnc-DC, it has been reported to be correlated with immune response. However, the role of Wfdc21 in the pathogenesis of sepsis is still unknown. In the present study, we aimed to investigate the role of Wfdc21 in the pathogenesis of sepsis. MATERIAL AND METHODS The cecal ligation and puncture (CLP)-induced sepsis model was established in Balb/c mice. Animals were euthanized 4, 8, 16, or 24 h after CLP. The glycogen distribution in the kidney and liver was checked by Periodic acid-Schiff (PAS) staining...
June 14, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29900011/adjuvant-composition-and-delivery-route-shape-immune-response-quality-and-protective-efficacy-of-a-recombinant-vaccine-for-entamoeba-histolytica
#19
Mayuresh M Abhyankar, Mark T Orr, Susan Lin, Mohammed O Suraju, Adrian Simpson, Molly Blust, Tiep Pham, Jeffrey A Guderian, Mark A Tomai, James Elvecrog, Karl Pedersen, William A Petri, Christopher B Fox
Amebiasis caused by Entamoeba histolytic a is the third leading cause of parasitic mortality globally, with some 100,000 deaths annually, primarily among young children. Protective immunity to amebiasis is associated with fecal IgA and IFN-γ in humans; however, no vaccine exists. We have previously identified recombinant LecA as a potential protective vaccine antigen. Here we describe the development of a stable, manufacturable PEGylated liposomal adjuvant formulation containing two synthetic Toll-like receptor (TLR) ligands: GLA (TLR4) and 3M-052 (TLR7/8)...
2018: NPJ Vaccines
https://www.readbyqxmd.com/read/29899345/subtractive-proteomics-to-identify-novel-drug-targets-and-reverse-vaccinology-for-the-development-of-chimeric-vaccine-against-acinetobacter-baumannii
#20
Vandana Solanki, Vishvanath Tiwari
The emergence of drug-resistant Acinetobacter baumannii is the global health problem associated with high mortality and morbidity. Therefore it is high time to find a suitable therapeutics for this pathogen. In the present study, subtractive proteomics along with reverse vaccinology approaches were used to predict suitable therapeutics against A. baumannii. Using subtractive proteomics, we have identified promiscuous antigenic membrane proteins that contain the virulence factors, resistance factors and essentiality factor for this pathogenic bacteria...
June 13, 2018: Scientific Reports
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