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Jacob E Friedman, Evgenia Dobrinskikh, Alba Alfonso-Garcia, Alexander Fast, Rachel C Janssen, Taylor K Soderborg, Aimee L Anderson, Julie A Reisz, Angelo D'Alessandro, Daniel N Frank, Charles E Robertson, Becky A de la Houssaye, Linda K Johnson, David J Orlicky, Xiaoxin X Wang, Moshe Levi, Eric O Potma, Karim C El Kasmi, Karen R Jonscher
Increasingly, evidence suggests that exposure to maternal obesity creates an inflammatory environment in utero , exerting long-lasting postnatal signatures on the juvenile innate immune system and microbiome that may predispose offspring to development of fatty liver disease. We found that exposure to a maternal Western-style diet (WD) accelerated fibrogenesis in the liver of offspring and was associated with early recruitment of proinflammatory macrophages at 8-12 weeks and microbial dysbiosis as early as 3 weeks of age...
March 2018: Hepatology Communications
Jiaqi Gu, Lingchun Luo, Qian Wang, Songfan Yan, Jing Lin, Dan Li, Bingbing Cao, Hongxia Mei, Binyu Ying, Lu Bin, Fang Gao Smith, Sheng-Wei Jin
Inflammation always accompanies infection during sepsis. Mitochondrial dysfunction and the role of reactive oxygen species (ROS) produced by mitochondria have been proposed in the pathogenesis of sepsis. Maresins have protective and resolving effects in experimental models of infection. In the present study, we investigated the effects of maresin 1 (MaR1) on mitochondrial function in cecal ligation and puncture (CLP)-induced sepsis and sepsis patients to identify mechanisms underlying maresin 1-mediated stimulation of ROS in mitochondria...
February 21, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Nanshan Song, Yinquan Fang, Xiyang Sun, Qingling Jiang, Chenghuan Song, Miaomiao Chen, Jianhua Ding, Ming Lu, Gang Hu
β2-aderenergic receptor (β2AR) agonist, Salmeterol exhibits anti-inflammatory activities. However, the inhibitory effects of Salmeterol on inflammasome activation are elusive and the underlying mechanisms need to be explored. In this study, we established inflammatory model in primary bone marrow-derived macrophages (BMDM) from C57BL/6J mice and β-arrestin2 knockout (β-arrestin2 -/- ) mice in vitro. In vivo study by LPS intraperitoneally (i.p.) in C57BL/6J mice was carried out to ascertain its roles in systemic inflammation...
February 12, 2018: Biochemical Pharmacology
Hossam M H Shalaby
A bidirectional mode-division multiplexer (BMDM) with antireflection gratings is designed, and its performance in terms of S-parameters is presented. A BMDM can (de)multiplex three modes with only two waveguides and a Bragg grating. The impact of return losses on the performance of BMDMs is studied and antireflection gratings are designed to reduce their effects. A theoretical analysis of the proposed (de)multiplexer is developed based on the perturbative coupled-mode theory. Analytical expressions for the coupled-mode equations of the proposed device are obtained, taking into account the effects of return losses...
January 20, 2018: Applied Optics
Jin-Xin Zhao, Yan-Yan Yu, Sha-Sha Wang, Su-Ling Huang, Yu Shen, Xin-Hua Gao, Li Sheng, Jing-Ya Li, Ying Leng, Jia Li, Jian-Min Yue
Hongkonoids AD (1-4), the first example of ascorbylated terpenoids featuring a unique 5,5,5-fused tricyclic spiroketal butyrolactone moiety and diterpenoid-derived long chain, were isolated from Dysoxylum hongkongense. Their structures were unambiguously assigned by a combination of spectroscopic data, chemical degradation, X-ray crystallography, CD analysis, and total synthesis. The total syntheses of compounds 1-4 were effectively accomplished by a convergent strategy with the longest linear sequences of 12-14 steps and overall yields of 5...
February 2, 2018: Journal of the American Chemical Society
Wenbo Li, Wei Liu, Can Chen, Wenhui Fan, He Zhang, Wenjun Liu, Lei Sun
Cyclophilin A (CypA) is a member of peptidyl prolylisomerases (PPIase) family. CypA is best known as a ubiquitously distributed intracellular protein. It has also been shown to be secreted by cells in response to inflammatory stimuli and oxidative stress. Extracellular CypA (eCypA) interacts with CD147 to initiate inflammatory responses via recruiting leucocytes into inflamed tissue. Recombinant CypA was expressed in Escherichia coli and then purified using Superdex 75™ 16/60. The results of Real-time PCR and ELISA showed that the expression levels of proinflammatory cytokines, such as IL-1β, secreted by eCypA stimulated BMDM were significantly up-regulated, indicating that eCypA played an important role in promoting inflammatory responses...
January 25, 2018: Sheng Wu Gong Cheng Xue Bao, Chinese Journal of Biotechnology
Alyssa J Rolfe, Dale B Bosco, Erynn N Broussard, Yi Ren
Bone marrow-derived macrophages (BMDMs) are mature leukocytes that serve a critical physiological role as professional phagocytes capable of clearing a variety of particles. Normally, BMDMs are restricted from the central nervous system (CNS), but following an injury, they can readily infiltrate. Once within the injured CNS tissue, BMDMs are the primary cell type responsible for the clearance of injury-derived cellular debris, including large quantities of lipid rich myelin debris. The neuropathological ramifications of BMDM infiltration and myelin debris phagocytosis within the CNS are complex and not well understood...
December 30, 2017: Journal of Visualized Experiments: JoVE
Flor Torres-Juarez, Lousseine Touqui, Juan Leon-Contreras, Cesar Rivas-Santiago, Jose A Enciso-Moreno, Rogelio Hernández-Pando, Bruno Rivas-Santiago
Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis (Mtb). Innate immunity is the first line of defense against Mtb and malfunctions in any of its components is associated with the susceptibility to the disease. Epithelial products, such as host defence peptides (HDP) are the first molecules produced to counteract the infection. Although a wide variety of HDP are produced by epithelial cells only few of them have been studied during Mtb infection. Here, we assessed the expression and production of the HDPs: psoriasin, sPLA2-IIA and RNase 7 in airway epithelial cells (NCI-H292), type II pneumocytes (A549 cells) and monocytes-derived macrophages from human peripheral blood mononuclear cells (bMDM) and from the human cell line THP1(MDM) after Mtb in vitro infection...
January 16, 2018: Pathogens and Disease
Chih-Wei Ko, Daniel Counihan, Jing Wu, Maria Hatzoglou, Michelle A Puchowicz, Colleen M Croniger
Phosphoenolpyruvate carboxykinase (Pck1) is a metabolic enzyme that is integral to the gluconeogenic and glyceroneogenic pathway. However, the role of Pck1 in macrophage metabolism and function is unknown. Using stable isotopomer MS analysis in a mouse model with a myeloid cell specific Pck1 deletion, we show here that this deletion increases the proinflammatory phenotype in macrophages. Incubation of LPS-stimulated bone marrow derived macrophages (BMDM) with [U-13C] glucose revealed reduced [13C] labeling of citrate and malate and increased [13C] labeling of lactate in Pck1 deleted BMDMs...
January 9, 2018: Journal of Biological Chemistry
Mariela Castelblanco, Jérôme Lugrin, Driss Ehirchiou, Sonia Nasi, Isao Ishii, Alexander So, Fabio Martinon, Nathalie Busso
A variety of stimuli, including monosodium urate (MSU) crystals, activate the NLRP3 inflammasome, and this activation involves several molecular mechanisms including xanthine oxidase (XO) upregulation and mitochondrial dysfunction. Upon oligomerization of apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1 becomes active and cleaves the proinflammatory cytokine IL-1β into its active secreted form. Hydrogen sulfide (H2S), a gasotransmitter mainly produced by cystathionine γ-lyase (CSE) in macrophages, could modulate inflammation...
December 26, 2017: Journal of Biological Chemistry
Prashanth Chandramani-Shivalingappa, Mahesh Bhandari, Sarah A Wiechert, Jessica Gilbertie, Douglas E Jones, Brett A Sponseller
Rhodococcus equi (R. equi) is an intracellular macrophage-tropic pathogen with potential for causing fatal pyogranulomatous pneumonia in foals between 1 and 6 months of age. In this study, we sought to determine whether infection of macrophages with R. equi could lead to the induction of autophagy. Murine bone marrow derived macrophages (BMDM) were infected with R. equi for various time intervals and analyzed for upregulation of autophagy proteins and accumulation of autophagosomes relative to uninfected controls...
2017: Scientifica
Young-Hoon Kim, Jae-Rin Lee, Myong-Joon Hahn
Epithelial-stromal interaction 1 (EPSTI1) was first discovered as a gene induced in breast cancer epithelial cells by co-cultured stromal fibroblasts. There are many reports on the role of Epsti1 in cancer malignancy. Epsti1 is now well known in regulating cancer. Recently, the role of Epsti1 in the immune response has been reported; these reports suggest the role of Epsti1 in immune function, immune privilege, and autoimmune diseases. Furthermore, they show that Epsti1 is expressed in various types of immune cells...
February 5, 2018: Biochemical and Biophysical Research Communications
Ing-Jung Chen, Siow-Wey Hee, Chun-Hsing Liao, Shih-Yao Lin, Lynn Su, Chia-Tung Shun, Lee-Ming Chuang
Sepsis is a systemic inflammation accompanied by multi-organ dysfunction due to microbial infection. Prostaglandins and their metabolites have long been studied for their importance in regulating the innate immune response. 15-keto-PGE2 (15k-PGE2 ) is a prostaglandin E2 (PGE2 ) metabolite, whose further processing is catalyzed by prostaglandin reductase 2 (PTGR2). We showed disruption of the Ptgr2 gene in mice improves the survival rate under both LPS- and cecum ligation/puncture (CLP)-induced experimental sepsis...
February 1, 2018: Free Radical Biology & Medicine
Min Young Park, Hyung Sik Kim, Mingyu Lee, Byunghyun Park, Ha Young Lee, Eun Bee Cho, Jae Young Seong, Yoe-Sik Bae
Osteoclasts can be differentiated from bone marrow-derived macrophages (BMDM). They play a key role in bone resorption. Identifying novel molecules that can regulate osteoclastogenesis has been an important issue. In this study, we found that FAM19A5, a neurokine or brain-specific chemokine, strongly stimulated mouse BMDM, resulting in chemotactic migration and inhibition of RANKL-induced osteoclastogenesis. Expression levels of osteoclast-related genes such as RANK, TRAF6, OSCAR, TRAP, Blimp1, c-fos, and NFATc1 were markedly decreased by FAM19A5...
November 14, 2017: Scientific Reports
Jeremy Tetsuo Miyauchi, Michael D Caponegro, Danling Chen, Matthew K Choi, Melvin Li, Stella E Tsirka
Glioma-associated microglia and macrophages (GAM), which infiltrate high-grade gilomas, constitute a major cellular component of these lesions. GAM behavior is influenced by tumor-derived cytokines that suppress initial antitumorigenic properties, causing them to support tumor growth and to convert and suppress adaptive immune responses to the tumor. Mice that lack the transmembrane receptor neuropilin-1 (Nrp1), which modulates GAM immune polarization, exhibit a decrease in glioma volumes and neoangiogenesis and an increase in antitumorigenic GAM infiltrate...
February 1, 2018: Cancer Research
Sara Baldanta, Mercedes Fernández-Escobar, Rebeca Acín-Perez, Manuel Albert, Emilio Camafeita, Inmaculada Jorge, Jesús Vázquez, José Antonio Enríquez, Susana Guerra
The interferon (IFN)-stimulated gene 15 (ISG15) encodes one of the most abundant proteins induced by interferon, and its expression is associated with antiviral immunity. To identify protein components implicated in IFN and ISG15 signaling, we compared the proteomes of ISG15-/- and ISG15+/+ bone marrow derived macrophages (BMDM) after vaccinia virus (VACV) infection. The results of this analysis revealed that mitochondrial dysfunction and oxidative phosphorylation (OXPHOS) were pathways altered in ISG15-/- BMDM treated with IFN...
October 2017: PLoS Pathogens
Bernd Hewing, Antje Ludwig, Cristian Dan, Max Pötzsch, Carmen Hannemann, Andreas Petry, Dilyara Lauer, Agnes Görlach, Elena Kaschina, Dominik N Müller, Gert Baumann, Verena Stangl, Karl Stangl, Nicola Wilck
Management of protein homeostasis by the ubiquitin-proteasome system is critical for atherosclerosis development. Recent studies showed controversial results on the role of immunoproteasome (IP) subunit β5i/LMP7 in maintenance of protein homeostasis under cytokine induced oxidative stress. The present study aimed to investigate the effect of β5i/LMP7-deficiency on the initiation and progression of atherosclerosis as a chronic inflammatory, immune cell driven disease. LDLR(-/-)LMP7(-/-) and LDLR(-/-) mice were fed a Western-type diet for either 6 or 24 weeks to induce early and advanced stage atherosclerosis, respectively...
October 17, 2017: Scientific Reports
Carolyn J Loveridge, Rob J van 't Hof, Gemma Charlesworth, Ayala King, Ee Hong Tan, Lorraine Rose, Anna Daroszewska, Amanda Prior, Imran Ahmad, Michelle Welsh, Ernest J Mui, Catriona Ford, Mark Salji, Owen Sansom, Karen Blyth, Hing Y Leung
Extracellular signal-regulated protein kinase 5 (ERK5) has been implicated during development and carcinogenesis. Nkx3.1-mediated Cre expression is a useful strategy to genetically manipulate the mouse prostate. While grossly normal at birth, we observed an unexpected phenotype of spinal protrusion in Nkx3.1:Cre;Erk5 (fl/fl) (Erk5 (fl/fl)) mice by ~6-8 weeks of age. X-ray, histological and micro CT (µCT) analyses showed that 100% of male and female Erk5 (fl/fl) mice had a severely deformed curved thoracic spine, with an associated loss of trabecular bone volume...
October 16, 2017: Scientific Reports
Akane Tanaka, Joyce To, Bronwyn O'Brien, Sheila Donnelly, Maria Lund
BACKGROUND: Macrophages are key players in the initiation, perpetuation and regulation of both innate and adaptive immune responses. They largely perform these roles through modulation of the expression of genes, especially those encoding cytokines. Murine bone marrow derived macrophages (BMDMs) are commonly used as a model macrophage population for the study of immune responses to pro-inflammatory stimuli, notably lipopolysaccharide (LPS), which may be pertinent to the human situation...
October 3, 2017: BMC Immunology
Martin T Speth, Urska Repnik, Elisabeth Müller, Julia Spanier, Ulrich Kalinke, Alexandre Corthay, Gareth Griffiths
The attenuated live vaccine strain bacille Calmette-Guérin (BCG) is currently the only available vaccine against tuberculosis (TB), but is largely ineffective against adult pulmonary TB, the most common disease form. This is in part due to BCG's ability to interfere with the host innate immune response, a feature that might be targeted to enhance the potency of this vaccine. Here, we investigated the ability of chitosan-based nanoparticles (pIC-NPs) containing polyinosinic-polycytidylic acid (poly(I:C)), an inducer of innate immunity via Toll-like receptor 3 (TLR3), to enhance the immunogenicity of BCG in mouse bone marrow derived macrophages (BMDM) in vitro...
November 6, 2017: Molecular Pharmaceutics
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