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sepsis macrophage

Joshua Bloom, Shan Sun, Yousef Al-Abed
Macrophage migration inhibitory factor (MIF) has emerged as a promising drug target in diseases including sepsis, rheumatoid arthritis, and cancer. MIF has multiple properties that favor development of specific, targeted therapies: it is expressed broadly among human cells, has noted roles in diverse inflammatory and oncological processes, and has intrinsic enzymatic activity amenable to high-throughput screening. Despite these advantages, anti-MIF therapy remains well behind other cytokine-targeted therapeutics, with no small molecules in the pipeline for clinical development and anti-MIF antibodies only recently beginning clinical trials...
October 20, 2016: Expert Opinion on Therapeutic Targets
Osman Yeşilbaş, Hasan Serdar Kıhtır, Hamdi Murat Yıldırım, Nevin Hatipoğlu, Esra Şevketoğlu
BACKGROUND: Leptospirosis is a zoonotic infectious disease caused by pathogenic spirochetes of the genus Leptospira. Although it is usually asymptomatic and self-limited, severe potentially fatal illness accompanied by multi-organ failure may occur. CASE REPORT: Here we report an unusual case of severe leptospirosis successfully treated with continuous venovenous hemofiltration (CVVHF) and therapeutic plasma exchange (TPE). The patient presented with pericardial tamponade, renal failure and macrophage activation syndrome, and later suffered prolonged jaundice and sclerosing cholangitis during hospitalization in the pediatric intensive care unit (PICU)...
September 2016: Balkan Medical Journal
Grzegorz Majka, Grażyna Więcek, Małgorzata Śróttek, Klaudyna Śpiewak, Małgorzata Brindell, Joanna Koziel, Janusz Marcinkiewicz, Magdalena Strus
Translocation of bacteria, primarily Gram-negative pathogenic flora, from the intestinal lumen into the circulatory system leads to sepsis. In newborns, and especially very low birth weight infants, sepsis is a major cause of morbidity and mortality. The results of recently conducted clinical trials suggest that lactoferrin, an iron-binding protein that is abundant in mammalian colostrum and milk, may be an effective agent in preventing sepsis in newborns. However, despite numerous basic studies on lactoferrin, very little is known about how metal saturation of this protein affects a host's health...
October 18, 2016: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
Erica L Heipertz, Jourdan Harper, Wendy E Walker
IFN regulatory factor (IRF)3 plays a detrimental role in the cecal ligation and puncture (CLP) mouse model of sepsis. However, it is unclear which pathway activates IRF3 in this context. In this report we investigate two pathways that activate IRF3: the Stimulator of Interferon Genes (STING) pathway (which senses cytosolic DNA) and the TIR-domain-containing adapter-inducing interferon-β (TRIF) pathway (which sense dsRNA and LPS via Toll-like receptor (TLR) 3 and 4). Initially, we examine the impact of these pathways using a severe CLP model (∼90% mortality)...
October 17, 2016: Shock
Jia Shi, Jian-Bo Yu, Wei Liu, Dan Wang, Yuan Zhang, Li-Rong Gong, Shu-An Dong, Da-Quan Liu
Acute respiratory distress syndrome (ARDS) is one of the most devastating complications of sepsis lacking of effective therapy. Mitochondrial dynamics undergoing continuous fusion and fission play a crucial role in mitochondrial structure and function. Fis1, as a small protein located on the outer membrane of mitochondria, has been thought to be an important protein mediated mitochondrial fission. During ARDS, alveolar macrophages suffer from increased oxidative stress and apoptosis, and also accompanied by disrupted mitochondrial dynamics...
October 14, 2016: Experimental Cell Research
Feng Xu, Taoqun Wen, Feng Wang, Wentao Sang, Nan Zeng
CONTEXT: Several pharmacological studies have shown that cinnamicaldehyde (CA) has anti-inflammatory and anti-tumor effects, but no data show the effects of CA on the endotoxin poisoning. OBJECTIVE: In this work, the protective effect of CA in LPS-induced endotoxin poisoning mice was investigated. MATERIALS AND METHODS: Mice were randomly divided into normal, LPS, LPS +5 mg/kg dexamethasone (DEX), LPS +0.132 g/kg CA, and LPS +0.264 g/kg CA group...
October 18, 2016: Immunopharmacology and Immunotoxicology
Young Ha Ahn, Sunyoung Park, Jeong June Choi, Bo-Kyung Park, Kyung Hee Rhee, Eunjoo Kang, Soyeon Ahn, Chul-Ho Lee, Jong Soo Lee, Kyung-Soo Inn, Mi-La Cho, Sung-Hwan Park, Kyunghee Park, Hae Jung Park, Jae Hyun Lee, Jung Won Park, Nam Hoon Kwon, Hyunbo Shim, Byung Woo Han, Pilhan Kim, Joo-Youn Lee, Youngho Jeon, Jin Won Huh, Mirim Jin, Sunghoon Kim
The N-terminal truncated form of a protein synthesis enzyme, tryptophanyl-tRNA synthetase (mini-WRS), is secreted as an angiostatic ligand. However, the secretion and function of the full-length WRS (FL-WRS) remain unknown. Here, we report that the FL-WRS, but not mini-WRS, is rapidly secreted upon pathogen infection to prime innate immunity. Blood levels of FL-WRS were increased in sepsis patients, but not in those with sterile inflammation. FL-WRS was secreted from monocytes and directly bound to macrophages via a toll-like receptor 4 (TLR4)-myeloid differentiation factor 2 (MD2) complex to induce phagocytosis and chemokine production...
October 17, 2016: Nature Microbiology
Hajera Amatullah, Yuexin Shan, Brittany L Beauchamp, Patricia L Gali, Sahil Gupta, Tatiana Maron-Gutierrez, Edwin R Speck, Alison E Fox-Robichaud, Jennifer L Y Tsang, Shirley H J Mei, Tak W Mak, Patricia Rm Rocco, John W Semple, Haibo Zhang, Pingzhao Hu, John C Marshall, Duncan J Stewart, Mary-Ellen Harper, Patricia C Liaw, W Conrad Liles, Claudia C Dos Santos
RATIONALE & OBJECTIVES: Effective and rapid bacterial clearance is a fundamental determinant of outcome(s) in sepsis. DJ-1 is a well-established reactive oxygen species (ROS) scavenger. As cellular ROS status is pivotal to inflammation and bacterial killing, we determined the role of DJ-1 in bacterial sepsis. METHODS: We used cell and murine models with gain and loss of function experiments, plasma and cells from septic patients. MEASUREMENTS & RESULTS: Stimulation of bone marrow derived macrophages (BMM) with endotoxin resulted in increased DJ-1 mRNA and protein expression...
October 13, 2016: American Journal of Respiratory and Critical Care Medicine
Minchan Gil, Yun Kyu Kim, Sang Bum Hong, Kyung Jin Lee
Naringin, a flavanone glycoside extracted from various plants, has a wide range of pharmacological effects. In the present study, we investigated naringin's mechanism of action and its inhibitory effect on lipopolysaccharide-induced tumor necrosis factor-alpha and high-mobility group box 1 expression in macrophages, and on death in a cecal ligation and puncture induced mouse model of sepsis. Naringin increased heme oxygenase 1 expression in peritoneal macrophage cells through the activation of adenosine monophosphate-activated protein kinase, p38, and NF-E2-related factor 2...
2016: PloS One
Chikkamenahalli Lakshminarayana Lakshmikanth, Shancy Petsel Jacob, Avinash Kundadka Kudva, Calivarathan Latchoumycandane, Puttaraju Srikanta Murthy Yashaswini, Mosale Seetharam Sumanth, Cassiano F Goncalves-de-Albuquerque, Adriana R Silva, Sridevi Annapurna Singh, Hugo C Castro-Faria-Neto, Sandeep Kumble Prabhu, Thomas M McIntyre, Gopal Kedihithlu Marathe
The endotoxin lipopolysaccharide (LPS) promotes sepsis, but bacterial peptides also promote inflammation leading to sepsis. We found, intraperitoneal administration of live or heat inactivated E. coli JE5505 lacking the abundant outer membrane protein, Braun lipoprotein (BLP), was less toxic than E. coli DH5α possessing BLP in Swiss albino mice. Injection of BLP free of LPS purified from E. coli DH5α induced massive infiltration of leukocytes in lungs and liver. BLP activated human polymorphonuclear cells (PMNs) ex vivo to adhere to denatured collagen in serum and polymyxin B independent fashion, a property distinct from LPS...
October 4, 2016: Scientific Reports
Kambis Sadeghi, Lukas Wisgrill, Isabelle Wessely, Susanne C Diesner, Simone Schüller, Celia Dürr, Armando Heinle, Monika Sachet, Arnold Pollak, Elisabeth Förster-Waldl, Andreas Spittler
Toll-like receptors (TLR) are crucial sensors of microbial agents such as bacterial or viral compounds. These receptors constitute key players in the induction of inflammation, e.g. in septic or chronic inflammatory diseases. Colony-stimulating factors (CSFs) such as granulocyte-macrophage-CSF (GM-CSF) or granulocyte-CSF (G-CSF) have been extensively investigated in their capacity to promote myelopoiesis in febrile neutropenia or to overcome immunosuppression in patients suffering from sepsis-associated neutropenia or from monocytic immunoincompetence...
2016: PloS One
Weiyue Zheng, Masataka Umitsu, Ishaan Jagan, Charles W Tran, Noboru Ishiyama, Michael BeGora, Kiyomi Araki, Pamela S Ohashi, Mitsuhiko Ikura, Senthil K Muthuswamy
The polarity protein Scribble (SCRIB) regulates apical-basal polarity, directional migration and tumour suppression in Drosophila and mammals. Here we report that SCRIB is an important regulator of myeloid cell functions including bacterial infection and inflammation. SCRIB interacts directly with the NADPH oxidase (NOX) complex in a PSD95/Dlg/ZO-1 (PDZ)-domain-dependent manner and is required for NOX-induced reactive oxygen species (ROS) generation in culture and in vivo. On bacterial infection, SCRIB localized to phagosomes in a leucine-rich repeat-dependent manner and promoted ROS production within phagosomes to kill bacteria...
October 3, 2016: Nature Cell Biology
He Ma, Xiaohui Wang, Tuanzhu Ha, Ming Gao, Li Liu, Ruitao Wang, Kaijiang Yu, John H Kalbfleisch, Race L Kao, David L Williams, Chuanfu Li
BACKGROUND:  This study examined the effect of miR-125b on sepsis-induced cardiac dysfunction. METHODS:  Mouse hearts were transfected with lentivirus expressing miR-125b (LmiR-125b) seven days prior to cecal ligation and puncture (CLP) induced sepsis. Cardiac function was examined by echocardiography before and 6 hours after CLP (n=6/group). Survival outcome was monitored following CLP sepsis (n=12/group). RESULTS:  LmiR-125b transfection significantly attenuated CLP sepsis-induced cardiac dysfunction...
September 28, 2016: Journal of Infectious Diseases
Chun-Mu Miao, Xiao-Wei Jiang, Kun He, Pei-Zhi Li, Zuo-Jin Liu, Ding Cao, Zhi-Bing Ou, Jian-Ping Gong, Chang-An Liu, Yao Cheng
The nucleotide-binding and oligomerization domain-like receptor 3 (NLRP3) inflammasome participates in the pathogenesis of acute liver injury during sepsis. Bone marrow mesenchymal stem cells (BMSCs) attenuate sepsis through prostaglandin E 2 (PGE2) by increasing the interleukin-10 (IL-10) production of macrophages; moreover, NLRP3 inflammasome assembly is effectively regulated by IL-10 during infection. Whether BMSCs have an effect on the activation of the NLRP3 inflammasome and its underlying mechanism is unclear...
September 22, 2016: Immunology Letters
Navina L Chrobok, Claudia Sestito, Micha M M Wilhelmus, Benjamin Drukarch, Anne-Marie van Dam
Monocytes and macrophages are key players in inflammatory processes following an infection or tissue damage. Monocytes adhere and extravasate into the inflamed tissue, differentiate into macrophages, and produce inflammatory mediators to combat the pathogens. In addition, they take up dead cells and debris and, therefore, take part in the resolution of inflammation. The multifunctional enzyme tissue Transglutaminase (TG2, tTG) is known to participate in most of those monocyte- and macrophage-mediated processes...
September 22, 2016: Amino Acids
Jing Xu, Ke-Qi Wang, Wei-Heng Xu, Ying-Hua Li, Yang Qi, Hong-Yuan Wu, Jian-Zhong Li, Zhi-Gao He, Hong-Gang Hu, Yan Wang, Jun-Ping Zhang
BACKGROUND:  MASM, a novel derivative of matrine, has inhibitory effect on activation of macrophages, dendritic cells and hepatic stellate cells and binds to ribosomal protein S5 (RPS5). This study was designed to evaluate effect of MASM on murine established lethal sepsis and its mechanisms. METHODS:  Mouse peritoneal macrophages and RAW264.7 cells that were infected with recombinant lentiviruses encoding shRPS5 were incubated with lipopolysaccharides (LPS) in the absence or presence of MASM in vitro...
September 22, 2016: Journal of Infectious Diseases
Yu He, Wei Xia Du, Hong Yan Jiang, Qing Ai, Jinxing Feng, Zhengqiu Liu, Jia Lin Yu
BACKGROUND: Early onset sepsis (EOS) remains a major cause of mortality and morbidity in neonates, and traditional clinical markers effective for adults are less effective in these patients. This study aimed to assess the value of individual plasma biomarkers as well as biomarker combinations for predicting EOS in neonates. METHODS: This prospective study included 151 neonates with suspected EOS. Plasma levels of interleukin (IL)-27, IL-6, IL-8, tumor necrosis factor (TNF)-α, heat shock protein (HSP) 70, macrophage inflammatory protein (MIP)-1α, MIP-1β, granzyme B, and matrix metalloproteinase (MMP)-8 were measured through multiplex cytokine profiling and assessed along with C-reactive protein (CRP) and procalcitonin (PCT)...
September 19, 2016: Shock
Wenjun Yan, Aihao Ding, Ha-Jeong Kim, Hua Zheng, Fang Wei, Xiaojing Ma
Progranulin (PGRN) is a widely expressed, pleiotropic protein that is involved in diverse biological processes, including cellular proliferation, neuron development, and wound healing. However, the role of PGRN in the regulation of pathogen-induced systemic inflammation and the mechanisms involved have not been established. In this study, we show that PGRN-deficient mice display heightened mortality in models of polymicrobial sepsis and endotoxinemia, with increased tissue levels of inflammatory cytokines and reduced IL-10 production...
September 12, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Liyun Xu, Peiqing Zhao, Yong Xu, Lishuang Gao, Hongxing Wang, Xiaoxia Jia, Hongxin Ma, Xiaoxong Liang, Chunxong Ma, Lifen Gao
Endotoxic shock is the primary cause of morbidity and mortality in hospital patients, creating an urgent need to explore the mechanisms involved in sepsis. Our previous studies showed that T-cell immunoglobulin- and mucin-domain-containing molecule-4 (Tim-4) attenuated the inflammatory response through regulating the functions of macrophages. However, the mechanism by which Tim-4 does this has not been fully elucidated. In this study, we found that Tim-4 expression was increased in lipopolysaccharide (LPS)-induced endotoxic shock...
September 12, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
Doreen E Szollosi, Ola A M Ghoneim, Mohammed K Manzoor, Jyothi Dhuguru, Ivan O Edafiogho
Pro-inflammatory mediators including TNF-alpha, IL-6, and nitric oxide are important for the regulation of the immune response when an infection is present, but when overproduced, it can be responsible for the development of tissue and organ injury seen in sepsis, as well as severe asthma, and autoimmune diseases such as Crohn's disease and rheumatoid arthritis. Data from our lab to characterize the novel compound enaminone E121 have suggested that macrophages stimulated with lipopolysaccharide (LPS) release significantly decreased levels of TNF-alpha and IL-6 as measured by enzyme-linked immunosorbent assay as compared to the DMSO control group...
September 10, 2016: Inflammation
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