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https://www.readbyqxmd.com/read/27902475/osthole-protects-sepsis-induced-acute-kidney-injury-via-down-regulating-nf-%C3%AE%C2%BAb-signal-pathway
#1
Chen Yu, Peng Li, Dong Qi, Lei Wang, Hong-Lin Qu, Yue-Juan Zhang, Xue-Kai Wang, Hua-Ying Fan
BACKGROUND AND PURPOSE: As a natural coumarin derivative from the Cnidium monnieri(L)Cusson fruit, osthole consists of 7-methoxy-8-isopentenoxy-coumarin. The purpose of this research is to study the mechanism and effect of osthole on sepsis-induced acute kidney injury. EXPERIMENTAL APPROACH: The protective effect of osthole on mouse macrophage RAW 264.7 and HK-2 cells induced by LPS in vitro and on acute kidney injury model induced by sepsis and established by puncture and cecal ligation (CLP) in vivo were tested...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27878656/mille-modis-morimur-we-die-in-a-thousand-ways
#2
Gaspar Banfalvi
Dying cells subjected to apoptotic programs are engulfed by neighboring cells or by professional phagocytes, without inflammation or immunological reactions in the tissue where apoptosis takes place. Apoptotic cells release danger-associated project signals to their neighbours, through different molecular patterns, stimulate antigen production and immune responses. Microenvironmental effects with several functional consequences indicate that cell death is a complex process and may take place in several ways...
November 23, 2016: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/27865166/ethyl-pyruvate-inhibits-the-acetylation-and-release-of-hmgb1-via-effects-on-sirt1-stat-signaling-in-lps-activated-raw264-7-cells-and-peritoneal-macrophages
#3
Young Min Kim, Eun Jung Park, Jung Hwan Kim, Sang Won Park, Hye Jung Kim, Ki Churl Chang
High mobility group box 1 (HMGB1), a cytokine present in the late phase of sepsis, may be a potential target for the treatment of sepsis. For HMGB1 to be actively secreted from macrophages during infections, it must be post-translationally modified. Although ethyl pyruvate (EP), a simple aliphatic ester derived from pyruvic acid, has been shown to inhibit the release of HMGB1 in lipopolysaccharide (LPS)-treated RAW 264.7 cells, the underlying mechanism(s) are not yet clear. We investigated the hypothesis that the upregulation of SIRT1 by EP might promote the deacetylation of HMGB1, which reduces HMGB1 release in LPS-activated macrophages...
November 16, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27860279/targeting-myeloid-differentiation-protein-2-by-the-new-chalcone-l2h21-protects-lps-induced-acute-lung-injury
#4
Yali Zhang, Tingting Xu, Beibei Wu, Hongjin Chen, Zheer Pan, Yi Huang, Liqin Mei, Yuanrong Dai, Xing Liu, Xiaoou Shan, Guang Liang
Acute inflammatory diseases are the leading causes of mortality in intensive care units. Myeloid differentiation 2 (MD-2) is required for recognizing lipopolysaccharide (LPS) by toll-like receptor 4 (TLR4), and represents an attractive therapeutic target for LPS-induced inflammatory diseases. In this study, we report a chalcone derivative, L2H21, as a new MD2 inhibitor, which could inhibit LPS-induced inflammation both in vitro and in vivo. We identify that L2H21 as a direct inhibitor of MD-2 by binding to Arg(90) and Tyr(102) residues in MD-2 hydrophobic pocket using a series of biochemical experiments, including surface plasmon response, molecular docking and amino acid mutation...
November 18, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27855617/eryptosis-ally-or-enemy
#5
Marilena Briglia, Maria Antonia Rossi, Caterina Faggio
Prior to senescence, erythrocytes may, experience injury which compromises their integrity and thus triggers suicidal erythrocyte death or eryptosis. This mechanism is characterised by cell shrinkage, cell membrane blebbing, and cell membrane phospholipid scrambling after phosphatidylserine exposure on the cell surface that is identified by macrophages which engulf and degrade the eryptotic cells. The term eryptosis also includes typical mechanisms, which contribute to the triggering of this process. Among them: oxidative stress, Ca2+ entry with an increase in cytosolic Ca2+ activity ([Ca ]i) and the activation of p38 kinase, which is a kinase expressed in human erythrocytes and activated after hyperosmotic shock...
November 18, 2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27849678/fc-gamma-receptor-iib-deficient-mice-a-lupus-model-with-increased-endotoxin-tolerance-related-sepsis-susceptibility
#6
Thunnicha Ondee, Saowapha Surawut, Sujittra Taratummarat, Nattiya Hirankan, Tanapat Palaga, Prapaporn Pisitkun, Trairak Pisitkun, Asada Leelahavanichkul
Hyper-elevated immune response of FcGRIIb-/- mice, a lupus model with an inhibitory-signaling defect, can become exhausted (less subsequent immune-response than the first response) with sequential LPS stimulation. Endotoxin tolerance-related modifications of inflammatory response were investigated in FcGRIIb-/- mice in both an in vivo sepsis model and in vitro using cultured macrophages. Serum cytokine concentrations, after the second LPS injection (at 5-fold higher levels than the first dose) did not exceed the first dose levels in either FcGRIIb-/- or wild-type mice...
November 15, 2016: Shock
https://www.readbyqxmd.com/read/27846826/natural-product-htp-screening-for-antibacterial-e-coli-0157-h7-and-anti-inflammatory-agents-in-lps-from-e-coli-o111-b4-activated-macrophages-and-microglial-cells-focus-on-sepsis
#7
Elizabeth A Mazzio, Nan Li, David Bauer, Patricia Mendonca, Equar Taka, Mohammed Darb, Leeshawn Thomas, Henry Williams, Karam F A Soliman
BACKGROUND: Acute systemic inflammatory response syndrome arising from infection can lead to multiple organ failure and death, with greater susceptibility occurring in immunocompromised individuals. Moreover, sub-acute chronic inflammation is a contributor to the pathology of diverse degenerative diseases (Parkinson's disease, Alzheimer's disease and arthritis). Given the known limitations in Western medicine to treat a broad range of inflammatory related illness as well as the emergence of antibiotic resistance, there is a renewed interest in complementary and alternative medicines (CAMs) to achieve these means...
November 15, 2016: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/27836913/immunoreceptor-cd300a-on-mast-cells-and-dendritic-cells-regulates-neutrophil-recruitment-in-a-murine-model-of-sepsis
#8
Kankanam Gamage Sanath Udayanga, Yoshiyuki Nakamura, Chigusa Nakahashi-Oda, Akira Shibuya
Sepsis is a life-threatening syndrome caused by abnormal host immune responses against bacterial infection. Although innate immune cells are known to be important in the pathogenesis of sepsis, how their activation is regulated during sepsis remains incompletely understood. Here we examined the role of the inhibitory immunoreceptor CD300a, which is expressed on various types of myeloid cells, in the pathogenesis of sepsis induced by cecal ligation and puncture (CLP). To this end, we used mice in which CD300a was specifically deleted on mast cells (MCs; Cd300a(fl/fl) Mcpt5-Cre), dendritic cells (DCs; Cd300a(fl/fl) Itgax-Cre), or macrophages and neutrophils (Cd300a(fl/fl) Lyz2-Cre)...
November 11, 2016: International Immunology
https://www.readbyqxmd.com/read/27831908/diagnosing-haemophagocytic-syndrome
#9
REVIEW
Ethan S Sen, Colin G Steward, Athimalaipet V Ramanan
Haemophagocytic syndrome, or haemophagocytic lymphohistiocytosis (HLH), is a hyperinflammatory disorder characterised by uncontrolled activation of the immune system. It can result from mutations in multiple genes involved in cytotoxicity or occur secondary to a range of infections, malignancies or autoimmune rheumatic diseases. In the latter case, it is also known as macrophage activation syndrome (MAS). Characteristic features are persistent fever, hepatosplenomegaly, petechial/purpuric rash, progressive cytopenias, coagulopathy, transaminitis, raised C reactive protein, falling erythrocyte sedimentation rate, hypertriglyceridaemia, hypofibrinogenaemia and extreme hyperferritinaemia often associated with multi-organ impairment...
October 24, 2016: Archives of Disease in Childhood
https://www.readbyqxmd.com/read/27821769/protein-aggregation-as-a-cellular-response-to-oxidative-stress-induced-by-heme-and-iron
#10
Luiz R C Vasconcellos, Fabianno F Dutra, Mariana S Siqueira, Heitor A Paula-Neto, Jennifer Dahan, Ellen Kiarely, Leticia A M Carneiro, Marcelo T Bozza, Leonardo H Travassos
Hemolytic diseases include a variety of conditions with diverse etiologies in which red blood cells are destroyed and large amounts of hemeproteins are released. Heme has been described as a potent proinflammatory molecule that is able to induce multiple innate immune responses, such as those triggered by TLR4 and the NLRP3 inflammasome, as well as necroptosis in macrophages. The mechanisms by which eukaryotic cells respond to the toxic effects induced by heme to maintain homeostasis are not fully understood, however...
November 7, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27816450/il-37-impairs-host-resistance-to-listeria-infection-by-suppressing-macrophage-function
#11
Mengmeng Zhao, Yongguang Hu, Juanjuan Shou, Shao Bo Su, Jianhua Yang, Tianshu Yang
Listeria monocytogenes is a Gram-positive intracellular bacterium that was transmitted through contaminated food and causes sepsis and even death. IL-37 has been described as an important anti-inflammatory factor, but little is known about the function of IL-37 in host defense against Liseria monocytogenes (Lm) infection. In mice model of systemic infection, we found that mice treated with IL-37 were more sensitive to Lm infection compared with PBS-treated mice. This reduced resistance to Lm in IL-37-treated mice is accompanied with increased bacterial burden and liver damage...
November 2, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27815380/interleukin-36%C3%AE-attenuates-sepsis-by-enhancing-antibacterial-functions-of-macrophages
#12
Xintong Tao, Zhixin Song, Chuanjiang Wang, Hongchun Luo, Qin Luo, Xue Lin, Liping Zhang, Yibing Yin, Ju Cao
BACKGROUND:  Sepsis is newly defined as life-threatening organ dysfunction caused by a dysregulated host response to infection with a high mortality rate and limited effective treatments, the role of interleukin-36α (IL-36α) in host response during sepsis remains unknown. METHODS:  An experimental sepsis model of cecal ligation and puncture (CLP) was established to investigate the effects of IL-36α on host response to sepsis. RESULTS:  IL-36α production was significantly up-regulated during sepsis...
November 3, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27812336/piperine-suppresses-pyroptosis-and-interleukin-1%C3%AE-release-upon-atp-triggering-and-bacterial-infection
#13
Yi-Dan Liang, Wen-Jing Bai, Chen-Guang Li, Li-Hui Xu, Hong-Xia Wei, Hao Pan, Xian-Hui He, Dong-Yun Ouyang
Piperine is a phytochemical present in black pepper (Piper nigrum Linn) and other related herbs, possessing a wide array of pharmacological activities including anti-inflammatory effects. Previously, we demonstrated that piperine has therapeutic effects on bacterial sepsis in mice, but the underlying mechanism has not been fully elucidated. In this study, we aimed to investigate the influences of piperine on pyroptosis in murine macrophages. The results showed that piperine dose-dependently inhibited ATP-induced pyroptosis, thereby suppressing interleukin-1β (IL-1β) or high mobility group box-1 protein (HMGB1) release in LPS-primed bone marrow-derived macrophages and J774A...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27794168/cd46-accelerates-macrophage-mediated-host-susceptibility-to-meningococcal-sepsis-in-a-murine-model
#14
Xiao Wang, Ding Zhang, Mikael Sjölinder, Yi Wan, Hong Sjölinder
CD46, a membrane cofactor expressed on all nucleated human cells, plays an essential role in suppressing autoimmune reactions and protecting host cells from complement-mediated attack. Human transgenic CD46 homozygous mice (CD46(+/+) ) are prone to lethal sepsis upon infection with Neisseria meningitidis (N. meningitidis). However, the underlying mechanisms are poorly understood. Here, we determined that CD46(+/+) mice produce large numbers of M1 type macrophages with enhanced surface expression of MHC II and production of pro-inflammatory mediators such as IL-6, TNF, IL-12, and IL-1β In the presence of M-CSF or GM-CSF, CD46 signaling enhances monocyte-macrophage differentiation...
October 28, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27792045/transient-receptor-potential-melastatin-2-regulates-phagosome-maturation-and-is-required-for-bacterial-clearance-in-escherichia-coli-sepsis
#15
ZhanQin Zhang, Ping Cui, Kai Zhang, QiXing Chen, XiangMing Fang
BACKGROUND: Transient receptor potential melastatin 2 is a Ca-permeable cation channel abundantly expressed in macrophages. Trpm2 mice showed exacerbated infection and mortality during polymicrobial sepsis, which is associated with inefficient bacterial killing in macrophages. However, the mechanism of transient receptor potential melastatin 2 regulating bacterial killing remains unknown. METHODS: Trpm2 mice were intraperitoneally injected with Escherichia coli...
October 28, 2016: Anesthesiology
https://www.readbyqxmd.com/read/27791478/differing-mechanisms-of-surviving-phagosomal-stress-among-group-b-streptococcus-strains-of-varying-genotypes
#16
Michelle L Korir, Clare Laut, Lisa M Rogers, Jessica A Plemmons, David M Aronoff, Shannon D Manning
Group B Streptococcus (GBS), a leading cause of neonatal sepsis and meningitis, asymptomatically colonizes up to 30% of women and can persistently colonize even after antibiotic treatment. Previous studies have shown that GBS resides inside macrophages, but the mechanism by which it survives remains unknown. Here, we examined the ability of 4 GBS strains to survive inside macrophages and then focused on 2 strains belonging to sequence type (ST)-17 and ST-12, to examine persistence in the presence of antibiotics...
October 28, 2016: Virulence
https://www.readbyqxmd.com/read/27790644/hemozoin-regulates-inos-expression-by-modulating-the-transcription-factor-nf-%C3%AE%C2%BAb-in-macrophages
#17
Ravi Ranjan, Manjula Karpurapu, Asha Rani, Athar H Chishti, John W Christman
Hemozoin (Hz) is released from ruptured erythrocytes during malaria infection caused by Plasmodium sp., in addition the malaria infected individuals are prone to bacterial sepsis. The molecular interactions between Hz, bacterial components and macrophages remains poorly investigated. In this report, we investigated the combinatorial immune-modulatory effects of phagocytosed Hz, Interferon gamma (IFNγ) or lipopolysaccharide (LPS) in macrophages. Macrophages were treated with various concentrations of commercial synthetic Hz, and surprisingly it did not result in inducible nitric oxide synthase (iNOS) expression...
2016: Biochemistry & Molecular Biology Journal
https://www.readbyqxmd.com/read/27789087/adipose-tissue-at-the-nexus-of-systemic-and-cellular-immunometabolism
#18
REVIEW
Ayano C Kohlgruber, Nelson M LaMarche, Lydia Lynch
At the simplest interpretation of the word, Immunometabolism describes the intersection of the fields of immunology and metabolism. With rapidly growing interest in this field, the term has expanded, and now encompasses a variety of concepts and definitions shaped by an individual's scientific area of expertise, cell-type and tissue of interest, and biological approach. One scientist may be interested in investigating the intrinsic metabolic checkpoints that drive a M1 versus M2 macrophage response, while another may be interested in how macrophages affect systemic metabolism during obesity...
October 24, 2016: Seminars in Immunology
https://www.readbyqxmd.com/read/27785087/adiponectin-treatment-attenuates-inflammatory-response-during-early-sepsis-in-obese-mice
#19
XianFeng Wang, Nancy L Buechler, Barbara K Yoza, Charles E McCall, Vidula Vachharajani
BACKGROUND: Morbid obesity increases the cost of care in critically ill patients. Sepsis is the leading cause of death in noncoronary intensive care units. Circulating cell-endothelial cell interactions in microcirculation are the rate-determining factors in any inflammation; obesity increases these interactions further. Adiponectin deficiency is implicated in increased cardiovascular risk in obese patients. We have shown that adiponectin deficiency increases microvascular dysfunction in early sepsis...
2016: Journal of Inflammation Research
https://www.readbyqxmd.com/read/27779186/pkm2-dependent-glycolysis-promotes-nlrp3-and-aim2-inflammasome-activation
#20
Min Xie, Yan Yu, Rui Kang, Shan Zhu, Liangchun Yang, Ling Zeng, Xiaofang Sun, Minghua Yang, Timothy R Billiar, Haichao Wang, Lizhi Cao, Jianxin Jiang, Daolin Tang
Sepsis, severe sepsis and septic shock are the main cause of mortality in non-cardiac intensive care units. Immunometabolism has been linked to sepsis; however, the precise mechanism by which metabolic reprogramming regulates the inflammatory response is unclear. Here we show that aerobic glycolysis contributes to sepsis by modulating inflammasome activation in macrophages. PKM2-mediated glycolysis promotes inflammasome activation by modulating EIF2AK2 phosphorylation in macrophages. Pharmacological and genetic inhibition of PKM2 or EIF2AK2 attenuates NLRP3 and AIM2 inflammasomes activation, and consequently suppresses the release of IL-1β, IL-18 and HMGB1 by macrophages...
October 25, 2016: Nature Communications
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