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https://www.readbyqxmd.com/read/28209510/microarray-and-transcription-binding-site-analysis-reveals-that-melatonin-attenuates-immune-responses-and-modulates-actin-rearrangement-in-macrophages
#1
Miki Kadena, Yutaro Kumagai, Alexis Vandenbon, Hitomi Matsushima, Haruka Fukamachi, Noboru Maruta, Hideo Kataoka, Takafumi Arimoto, Hirobumi Morisaki, Takahiro Funatsu, Hirotaka Kuwata
Melatonin produced by the pineal gland suppresses inflammatory responses in innate immune cells. However, the mechanism of how melatonin affects inflammatory gene regulation remains unclear. Here we performed comprehensive microarray analysis combined with transcription factor binding site (TFBS) analysis using LPS-induced mouse macrophages to investigate the effect of melatonin treatment. The results showed that melatonin preferentially downregulated interferon regulatory factors (IRFs) and signal transducers and activators of transcription (STATs) related signaling...
February 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28187742/regulatory-role-of-cytosolic-phospholipase-a2-alpha-in-the-induction-of-cd40-in-microglia
#2
Yafa Fetfet Malada-Edelstein, Nurit Hadad, Rachel Levy
BACKGROUND: The aberrant expression of CD40, a co-stimulatory receptor found on the antigen-presenting cells, is involved in the pathogenesis of various degenerative diseases. Our previous study demonstrated that the reduction of cytosolic phospholipase A2 alpha (cPLA2α) protein overexpression and activation in the spinal cord of a mouse model of ALS, hmSOD1 G93A, inhibited CD40 upregulation in microglia. The present study was designed to determine whether cPLA2α has a direct, participatory role in the molecular events leading to CD40 induction...
February 10, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28167474/regulatory-effect-of-caspase-11-on-interleukin-1%C3%AE-in-the-fungal-keratitis
#3
Keke Zhu, Hongmei Mu, Baimu Pi
Caused by fungus, fungal keratitis is a kind of infections corneal disease with high rate of blindness, which patients are mainly farmers in developing countries. Interleukin, as important proinflammatory cytokines, involve in immune defense process against fungal infection of cornea. The expression of interleukin in the pathogenesis of fungal keratitis, especially the main source of its cells, is not clear and the cell signaling pathways which regulate the synthesis and modification of interleukin is still unknown...
November 2016: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28165624/myeloid-myd88-contributes-to-ethanol-induced-liver-injury-in-mice-linking-hepatocellular-death-to-inflammation
#4
Hao Zhou, Minja Yu, Sanjoy Roychowdhury, Carlos Sanz-Garcia, Katherine A Pollard, Megan R McMullen, Xiuli Liu, Xiaoxia Li, Laura E Nagy
BACKGROUND: Toll-like receptor 4 (TLR4) is critical for ethanol-induced liver injury. TLR4 signaling is mediated by two proximal adaptor molecules: myeloid differentiation primary-response protein (MyD88) and TLR-domain-containing adapter-inducing interferon-β (TRIF). Studies utilizing global knock-outs of MyD88 and TRIF identified a predominant role for TRIF signaling in the progression of ethanol-induced liver injury. In contrast, IL1 receptor, which signals solely via the MyD88 pathway, is also known to mediate ethanol-induced liver injury...
February 6, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28138020/the-type-ii-secretion-system-of-legionella-pneumophila-dampens-the-myd88-and-tlr2-signaling-pathway-in-infected-human-macrophages
#5
Celeste A Mallama, Kessler McCoy-Simandle, Nicholas P Cianciotto
Previously, we reported that mutants of L. pneumophila lacking a type II secretion (T2S) system elicit higher levels of cytokines (e.g., IL-6) following infection of U937 cells, a human macrophage-like cell line. We now show that this effect of T2S is also manifest upon infection of human THP-1 cell macrophages and peripheral blood monocytes but does not occur during infection of murine macrophages. Supporting the hypothesis that T2S acts to dampen the triggering of an innate immune response, we observed that the mitogen-activated protein kinase (MAPK) and nuclear transcription factor kappa-B (NF-κB) pathways are more highly stimulated upon infection with the T2S mutant compared to wild-type...
January 30, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28134560/chloroquine-attenuates-lipopolysaccharide-induced-inflammatory-responses-through-upregulation-of-usp25
#6
Changyu Ding, Fangfang Li, Yupeng Long, Jiang Zheng
Lipopolysaccharide (LPS) is a key pathogenic factor in sepsis, and its recognition by toll-like receptor 4 (TLR4) can activate two district signaling pathways, leading to activation of transcription factors including NF-κB and interferon regulatory factor 3 (IRF3). Chloroquine (CQ) has been shown to affect LPS-TLR4 colocalization and inhibit both MyD88-dependent and TRAM/TRIF-dependent pathways, though the mechanism involved is still poorly understood. Here, we found that the ubiquitin-proteasome system might be involved in this process...
November 30, 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28123321/in%C3%A2-vitro-antioxidative-and-anti-inflammatory-effects-of-the-compound-k-rich-fraction-biogf1k-prepared-from-panax-ginseng
#7
Muhammad Jahangir Hossen, Yong Deog Hong, Kwang-Soo Baek, Sulgi Yoo, Yo Han Hong, Ji Hye Kim, Jeong-Oog Lee, Donghyun Kim, Junseong Park, Jae Youl Cho
BACKGROUND: BIOGF1K, a compound K-rich fraction prepared from the root of Panax ginseng, is widely used for cosmetic purposes in Korea. We investigated the functional mechanisms of the anti-inflammatory and antioxidative activities of BIOGF1K by discovering target enzymes through various molecular studies. METHODS: We explored the inhibitory mechanisms of BIOGF1K using lipopolysaccharide-mediated inflammatory responses, reporter gene assays involving overexpression of toll-like receptor adaptor molecules, and immunoblotting analysis...
January 2017: Journal of Ginseng Research
https://www.readbyqxmd.com/read/28120431/central-role-of-the-tir-domain-containing-adaptor-inducing-interferon-%C3%AE-trif-adaptor-protein-in-murine-sterile-liver-injury
#8
Katherine J Brempelis, Sebastian Y Yuen, Nicole Schwarz, Isaac Mohar, Ian N Crispe
: Multiple pathways drive the sterile injury response in the liver; however, it is unclear how the type of cells injured or the mechanism of injury activates these pathways. Here, we use a model of selective hepatocyte death to investigate sterile liver injury. In this model, the TIR-domain-containing adaptor-inducing interferon-β (TRIF) was a central mediator of the resulting intrahepatic inflammatory response that was independent of both upstream Toll-like receptor (TLR) 4 signaling and downstream type I IFN signaling...
January 24, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28056977/corilagin-ameliorates-the-extreme-inflammatory-status-in-sepsis-through-tlr4-signaling-pathways
#9
Hua-Rong Li, Jie Liu, Shu-Ling Zhang, Tao Luo, Fei Wu, Ji-Hua Dong, Yuan-Jin Guo, Lei Zhao
BACKGROUND: Sepsis is one of the serious disorders in clinical practice. Recent studies found toll-like receptors 4 (TLR4) played an important role in sepsis. In this study, we tried to find the influence of Corilagin on TLR4 signal pathways in vitro and in vivo. METHODS: The cellular and animal models of sepsis were established by LPS and then interfered with Corilagin. Real-time PCR and western blot were employed to detect the mRNA and protein expressions of TLR4, MyD88, TRIF and TRAF6...
January 5, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28052863/double-stranded-rna-up-regulates-the-expression-of-inflammatory-mediators-in-human-aortic-valve-cells-through-the-tlr3-trif-non-canonical-nf-%C3%AE%C2%BAb-pathway
#10
Qiong Zhan, Rui Song, Fei Li, Lihua Ao, Qingchun Zeng, Dingli Xu, David A Fullerton, Xianzhong Meng
BACKGROUND: Calcific aortic valve disease (CAVD) is a chronic inflammatory condition and the inflammatory responses of aortic valve interstitial cells (AVICs) play a critical role in the disease progression. Double-stranded RNA (dsRNA) released from damaged or stressed cells is pro-inflammatory and may contribute to the mechanism of chronic inflammation observed in diseased aortic valves. The objective of this study is to determine the effect of dsRNA on AVIC inflammatory responses and the underlying mechanism...
January 4, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28049762/the-tyrosine-kinase-src-promotes-phosphorylation-of-the-kinase-tbk1-to-facilitate-type-i-interferon-production-after-viral-infection
#11
Xuelian Li, Mingjin Yang, Zhou Yu, Songqing Tang, Lei Wang, Xuetao Cao, Taoyong Chen
Various pattern recognition receptors (PRRs) are activated in response to viral infection to stimulate the production of type I interferons (IFNs). However, central to the responses of all of these receptors is their activation of the kinase TBK1, which stimulates transcription by IFN regulatory factor 3 (IRF3). We investigated the mechanism by which the kinase activity of TBK1 is stimulated in response to viral infection. We found that the tyrosine kinase Src promoted the phosphorylation of TBK1 on Tyr(179) upon viral infection of RAW264...
January 3, 2017: Science Signaling
https://www.readbyqxmd.com/read/28049150/fosl1-inhibits-type-i-interferon-responses-to-malaria-and-viral-infections-by-blocking-tbk1-and-traf3-trif-interactions
#12
Baowei Cai, Jian Wu, Xiao Yu, Xin-Zhuan Su, Rong-Fu Wang
: Innate immune response plays a critical role in controlling invading pathogens, but such an immune response must be tightly regulated. Insufficient or overactivated immune responses may lead to harmful or even fatal consequences. To dissect the complex host-parasite interactions and the molecular mechanisms underlying innate immune responses to infections, here we investigate the role of FOS-like antigen 1 (FOSL1) in regulating the host type I interferon (IFN-I) response to malaria parasite and viral infections...
January 3, 2017: MBio
https://www.readbyqxmd.com/read/28011393/astragaloside-iv-attenuates-cognitive-impairments-induced-by-transient-cerebral-ischemia-and-reperfusion-in-mice-via-anti-inflammatory-mechanisms
#13
Min Li, Hongyan Li, Fang Fang, Xueyang Deng, Shiping Ma
Astragaloside IV (AS-IV) is the main active component isolated from the traditional Chinese medicinal herb Astragalus membranaceus. Studies have demonstrated that AS-IV has neuroprotective effects in cerebral ischemic models. In this study, we aimed to investigate the effects of AS-IV on memory impairment induced by transient cerebral ischemia and reperfusion in mice, as well as the associated signaling mechanisms. Severe memory deficits were induced by bilateral common carotid artery occlusion (BCCAO) in mice as indicated in the Morris water maze test in this study...
February 3, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28010888/dose-dependent-effects-of-morphine-on-lipopolysaccharide-lps-induced-inflammation-and-involvement-of-multixenobiotic-resistance-mxr-transporters-in-lps-efflux-in-teleost-fish
#14
Hélène Mottaz, Rene Schönenberger, Stephan Fischer, Rik I L Eggen, Kristin Schirmer, Ksenia J Groh
Opioid drugs, such as morphine (MO), detected in aquatic environments worldwide, may harm fish due to their semi-persistence and ability to potently interact with molecular targets conserved across vertebrates. Here, we established a waterborne bacterial lipopolysaccharide (LPS) challenge assay with zebrafish embryos as a model to investigate chemically-induced disruption of the innate immune system, and used it to study the effects of MO exposure. Exposure to 1 mg/L MO resulted in pronounced immunosuppression, reflected in downregulation of several inflammation-related genes, including myd88, trif, traf6, p38, nfκb2, il-1β, il-8 and ccl34a...
February 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28007523/pinocembrin-protects-hemorrhagic-brain-primarily-by-inhibiting-toll-like-receptor-4-and-reducing-m1-phenotype-microglia
#15
Xi Lan, Xiaoning Han, Qian Li, Qiang Li, Yufeng Gao, Tian Cheng, Jieru Wan, Wei Zhu, Jian Wang
Neuroinflammation is a major contributor to intracerebral hemorrhage (ICH) progression, but no drug is currently available to reduce this response and protect against ICH-induced injury. Recently, the natural product pinocembrin has been shown to ameliorate neuroinflammation and is undergoing a phase II clinical trial for ischemic stroke treatment. In this study, we examined the efficacy of pinocembrin in an ICH model, and further examined its effect on microglial activation and polarization. In vivo, pinocembrin dose-dependently reduced lesion volume by ∼47...
December 20, 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/27997892/the-role-of-tlr4-in-m1-macrophage-induced-epithelial-mesenchymal-transition-of-peritoneal-mesothelial-cells
#16
Jun Shi, Qing Li, Meixiao Sheng, Min Zheng, Manshu Yu, Lu Zhang
BACKGROUND/AIMS: Peritoneal fibrosis is a frequent complication of peritoneal dialysis that follows inflammation. It is recognized that epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells (PMCs), plays a key role in fibrogenesis. However, the relationship between inflammatory macrophages and PMCs remains elusive. In this study, we investigated the effects of different polarized macrophages on EMT of HMrSV5 PMCs. METHODS: Monocytes were polarized to M1/M2 macrophages before being added to HMrSV5 in direct or indirect contact...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27912060/the-hippo-pathway-kinases-lats1-2-suppress-cancer-immunity
#17
Toshiro Moroishi, Tomoko Hayashi, Wei-Wei Pan, Yu Fujita, Matthew V Holt, Jun Qin, Dennis A Carson, Kun-Liang Guan
Poorly immunogenic tumor cells evade host immunity and grow even in the presence of an intact immune system, but the complex mechanisms regulating tumor immunogenicity have not been elucidated. Here, we discovered an unexpected role of the Hippo pathway in suppressing anti-tumor immunity. We demonstrate that, in three different murine syngeneic tumor models (B16, SCC7, and 4T1), loss of the Hippo pathway kinases LATS1/2 (large tumor suppressor 1 and 2) in tumor cells inhibits tumor growth. Tumor regression by LATS1/2 deletion requires adaptive immune responses, and LATS1/2 deficiency enhances tumor vaccine efficacy...
December 1, 2016: Cell
https://www.readbyqxmd.com/read/27908440/lipid-raft-dependent-endocytosis-negatively-regulates-responsiveness-of-j774-macrophage-like-cells-to-lps-by-down-regulating-the-cell-surface-expression-of-lps-receptors
#18
Szczepan Józefowski, Małgorzata Śróttek
Acting through CD14 and TLR4/MD-2, lipopolysaccharide (LPS) triggers strong pro-inflammatory activation of macrophages, which, if not appropriately controlled, may lead to lethal septic shock. Therefore, numerous mechanisms of negative regulation of responses to LPS exist, but whether they include down-regulation of LPS receptors is not clear. We have found that in J774 cells, the clathrin-dependent endocytic pathway enables activation of TRIF-dependent TLR4 signaling within endosomes, but is not associated with the down-regulation of TLR4 or CD14 surface expression...
November 23, 2016: Cellular Immunology
https://www.readbyqxmd.com/read/27891130/molecular-mechanisms-that-underlie-the-dynamic-adaptation-of-innate-monocyte-memory-to-varying-stimulant-strength-of-tlr-ligands
#19
Ruoxi Yuan, Shuo Geng, Liwu Li
In adaptation to rising stimulant strength, innate monocytes can be dynamically programed to preferentially express either pro- or anti-inflammatory mediators. Such dynamic innate adaptation or programing may bear profound relevance in host health and disease. However, molecular mechanisms that govern innate adaptation to varying strength of stimulants are not well understood. Using lipopolysaccharide (LPS), the model stimulant of toll-like-receptor 4 (TLR4), we reported that the expressions of pro-inflammatory mediators are preferentially sustained in monocytes adapted by lower doses of LPS, and suppressed/tolerized in monocytes adapted by higher doses of LPS...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27881733/lysosomal-trafficking-regulator-lyst-links-membrane-trafficking-to-toll-like-receptor-mediated-inflammatory-responses
#20
Andreas Westphal, Weijia Cheng, Jinbo Yu, Guntram Grassl, Martina Krautkrämer, Otto Holst, Niko Föger, Kyeong-Hee Lee
Subcellular compartmentalization of receptor signaling is an emerging principle in innate immunity. However, the functional integration of receptor signaling pathways into membrane trafficking routes and its physiological relevance for immune responses is still largely unclear. In this study, using Lyst-mutant beige mice, we show that lysosomal trafficking regulator Lyst links endolysosomal organization to the selective control of toll-like receptor 3 (TLR3)- and TLR4-mediated proinflammatory responses. Consequently, Lyst-mutant mice showed increased susceptibility to bacterial infection and were largely resistant to endotoxin-induced septic shock...
January 2017: Journal of Experimental Medicine
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