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Kishore Das, Tima Thomas, Omar Garnica, Subramanian Dhandayuthapani
Tuberculosis continues to be a great cause of morbidity and mortality in different parts of the world. Unfortunately, the current BCG vaccine being administered is not fully protective against tuberculosis; therefore, there is a great need for alternate vaccines. With an aim to develop such vaccines, we have analyzed the utility of Bacillus subtilis spores for the expression of two major immunodominant antigens of Mycobacterium tuberculosis, Ag85B and CFP10. We created three recombinant B. subtilis strains to express a truncated fusion of Ag85B191-325 and CFP101-70 antigens (T85BCFP), either on the spore coat (MTAG1 strain) or in the cytosol of B...
September 28, 2016: Tuberculosis
Anne Kresinsky, Nadine Schneble, Caroline Schmidt, Adrian Frister, Reinhard Bauer, Reinhard Wetzker, Jörg P Müller
Due to their ability to phagocytise invading microbes macrophages play a key role in the innate and acquired immune system. In this article the role of phosphoinositide 3-kinase gamma (PI3Kγ) for phagocytosis was studied in bone marrow derived macrophages (BMDM). By using genetic and pharmacological approaches our data clearly demonstrate PI3Kγ is acting as a mediator of macrophage phagocytosis. Phagocytosis of LPS activated BMDM was reduced in PI3Kγ depleted primary BMDM or macrophage cell line J774. Depletion of other class I phosphoinositide 3-kinases did not alter phagocytic activity...
October 5, 2016: Immunology Letters
Vivian A Paschoal, Mariane T Amano, Thiago Belchior, Juliana Magdalon, Patricia Chimin, Maynara L Andrade, Milene Ortiz-Silva, Érique Castro, Alex S Yamashita, José Cesar Rosa Neto, Niels O Câmara, William T Festuccia
Genetic- and diet-induced obesity and insulin resistance are associated with an increase in mechanistic target of rapamycin complex (mTORC) 1 activity in adipose tissue. We investigated herein the effects of pharmacological mTORC1 inhibition in the development of adipose tissue inflammation induced by high-fat diet (HFD) feeding, as well as in the polarization, metabolism and function of bone marrow-derived macrophages (BMDM). For this, C57BL/6J mice fed with a standard chow diet or a HFD (60% of calories from fat) and treated with either vehicle (0...
September 28, 2016: Immunobiology
Purnima Gupta, Supriya Srivastav, Shriya Saha, Pijush K Das, Anindita Ukil
In order to establish infection, intra-macrophage parasite Leishmania donovani needs to inhibit host defense parameters like inflammatory cytokine production and apoptosis. In the present study, we demonstrate that the parasite achieves both by exploiting a single host regulator AKT for modulating its downstream transcription factors, β-catenin and FOXO-1. L. donovani-infected RAW264.7 and bone marrow-derived macrophages (BMDM) treated with AKT inhibitor or dominant negative AKT constructs showed decreased anti-inflammatory cytokine production and increased host cell apoptosis resulting in reduced parasite survival...
November 1, 2016: Cell Death and Differentiation
Saskia Maria Burm, Ella Alwine Zuiderwijk-Sick, Paola Massiel Weert, Jeffrey John Bajramovic
Under stressful conditions nucleotides are released from dying cells into the extracellular space, where they can bind to purinergic P2X and P2Y receptors. High concentrations of extracellular ATP in particular induce P2X7-mediated signaling, which leads to inflammasome activation. This in turn leads to the processing and secretion of pro-inflammatory cytokines, like interleukin (IL)-1β. During neurodegenerative diseases, innate immune responses are shaped by microglia and we have previously identified microglia-specific features of inflammasome-mediated responses...
September 19, 2016: Glia
Han Yao, Yunjiao Zhang, Liu Liu, Youcui Xu, Xi Liu, Jun Lin, Wei Zhou, Pengfei Wei, Peipei Jin, Long-Ping Wen
Lanthanide-based nanoparticles (LNs) hold great promise in medicine. A variety of nanocrystals, including LNs, elicits potent inflammatory response through activation of NLRP3 inflammasome. We have previously identified an LNs-specific surface coating peptide RE-1, with the sequence of 'ACTARSPWICG', which reduced nanocrystal-cell interaction and abrogated LNs-induced autophagy and toxicity in both HeLa cells and liver hepatocytes. Here we show that RE-1 coating effectively inhibited LNs-induced inflammasome activation, mostly mediated by NLRP3, in mouse bone marrow derived macrophage (BMDM) cells, human THP-1 cells and mouse peritoneal macrophages and also reduced LNs-elicited inflammatory response in vivo...
November 2016: Biomaterials
Haojun Yang, Haoming Zhou, Lin Zhuang, Xuehao Wang, Ling Lv
BACKGROUND: The G protein-coupled receptor TGR5 is a novel plasma membrane-bound G protein-coupled bile acid (BA) receptor. TGR5-induced liver protection has been demonstrated during several liver diseases, except during ischemia/reperfusion injury (IRI). METHOD: Male adult wild-type and TGR5 knockout mice were subjected to liver partial warm ischemia/reperfusion. Hepatic injury was evaluated based on serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST)...
September 6, 2016: Liver Transplantation
Yuan Gao, Yujie Huang, Yue Zhao, Yang Hu, Zhiyu Li, Qinglong Guo, Kai Zhao, Na Lu
LL202, a newly-synthesized flavonoid derivative, has been reported to inhibit inflammatory-induced angiogenesis. However, the exact role of LL202 in inflammation along with its mechanism has not been explored. In this study, we investigated the anti-inflammatory effect of LL202 on intestinal inflammation by establishing dextran sulfate sodium (DSS)-induced experimental colitis. LL202 attenuated DSS-induced body weight loss, colon length shortening and colonic pathological damage. The inflammatory cells infiltration, myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) activities were decreased by LL202 in a dose-dependent manner...
August 31, 2016: Oncotarget
Jae-Wook Lee, Sojin Park, Hye-Kyoung Han, Sung Hee Um, Eun-Yi Moon
Nonylphenol (NP) as well-known "endocrine disrupter" influences sexual and reproductive development. Here, we investigated the effect of NP on M1-/M2-type macrophages and their role in lipopolysaccharide (LPS)-induced sepsis. Polarized macrophages of M1- and M2-types were obtained by the treatment with LPS and interleukin-4 (IL-4) to bone marrow-derived macrophages (BMDM), respectively. Coincubation of M1-macrophages with NP decreased COX-2, iNOS, IL-6, and TNF-α expression but no changes were detected in the production of nitric oxide (NO)...
August 29, 2016: Environmental Toxicology
Yun-Xia Shao, Xin-Xing Xu, Yuan-Yuan Li, Xiang-Ming Qi, Kun Wang, Yong-Gui Wu, Xiao-Ming Meng
ETHNOPHARMACOLOGICAL RELEVANCE: Paeoniflorin(PF), extracted from the root peeled of Paeonia lactiflora Pall(Family: Ranunculaceae), has therapeutic potential in many animal models of inflammatory diseases. AIM OF THE STUDY: Although the anti-inflammatory efficacy of PF has been well illustrated in several animal models, whether it could attenuate diabetic nephropathy and detailed mechanisms are still obscure. Till now, accumulating evidence has proposed the pivotal role of toll-like receptors (TLRs) in renal inflammation in diabetic patients...
August 23, 2016: Journal of Ethnopharmacology
Lewis Taylor, Maximillian Hugo Brodermann, David McCaffary, Asif Jilani Iqbal, David R Greaves
Netrin-1, acting at its cognate receptor UNC5b, has been previously demonstrated to inhibit CC chemokine-induced immune cell migration. In line with this, we found that netrin-1 was able to inhibit CCL2-induced migration of bone marrow derived macrophages (BMDMs). However, whether netrin-1 is capable of inhibiting chemotaxis to a broader range of chemoattractants remains largely unexplored. As our initial experiments demonstrated that RAW264.7 and BMDMs expressed high levels of C5a receptor 1 (C5aR1) on their surface, we aimed to determine the effect of netrin-1 exposure on monocyte/macrophage cell migration induced by C5a, a complement peptide that plays a major role in multiple inflammatory pathologies...
2016: PloS One
Theodore S Kapellos, Lewis Taylor, Heyne Lee, Sally A Cowley, William S James, Asif J Iqbal, David R Greaves
Phagocytosis of pathogens, apoptotic cells and debris is a key feature of macrophage function in host defense and tissue homeostasis. Quantification of macrophage phagocytosis in vitro has traditionally been technically challenging. Here we report the optimization and validation of the IncuCyte ZOOM® real time imaging platform for macrophage phagocytosis based on pHrodo® pathogen bioparticles, which only fluoresce when localized in the acidic environment of the phagolysosome. Image analysis and fluorescence quantification were performed with the automated IncuCyte™ Basic Software...
September 15, 2016: Biochemical Pharmacology
Wenhan Wang, Zhong Li, Qingjuan Meng, Pei Zhang, Pengcheng Yan, Zhenbiao Zhang, Hao Zhang, Jingrui Pan, Yujia Zhai, Yaoge Liu, Xiaokai Wang, Weiwei Li, Yunpeng Zhao
It is well established that the tumor necrosis factor-α (TNF-α) plays a dominant role in rheumatoid arthritis (RA). Calcium channel is recently reported to be closely associated with various inflammatory diseases. However, whether chronic calcium channel blocker verapamil plays a role in RA still remains unknown. To investigate the role of verapamil in antagonizing TNF-α-mediated inflammation reaction and the underlying mechanisms, bone marrow-derived macrophages (BMDM) cells were cultured with stimulation of TNF-α, in the presence or absence of verapamil...
October 2016: Inflammation
Si-Yoon Kim, Eun-Jin Lim, Young-So Yoon, Young-Ho Ahn, Eun-Mi Park, Hee-Sun Kim, Jihee Lee Kang
Mer signaling increases the transcriptional activity of liver X receptor (LXR) to promote the resolution of acute sterile inflammation. Here, we aimed to understand the pathway downstream of Mer signaling after growth arrest-specific protein 6 (Gas6) treatment that leads to LXR expression and transcriptional activity in mouse bone-marrow derived macrophages (BMDM). Gas6-induced increases in LXRα and LXRβ and expression of their target genes were inhibited in BMDM from STAT1(-/-) mice or by the STAT1-specific inhibitor fludarabine...
2016: Scientific Reports
Huimin Deng, Zhengchao Li, Yafang Tan, Zhaobiao Guo, Yangyang Liu, Ye Wang, Yuan Yuan, Ruifu Yang, Yujing Bi, Yang Bai, Fachao Zhi
Commensal Bacteroides fragilis possesses immune-regulatory characteristics. Consequently, it has been proposed as a potential novel probiotic because of its therapeutic effects on immune imbalance, mental disorders and inflammatory diseases. Macrophages play a central role in the immune response, developing either a classical-M1 or an alternative-M2 phenotype after stimulation with various signals. The interactions between macrophages and B. fragilis, however, remain to be defined. Here, a new isolate of B...
2016: Scientific Reports
Ryan S McMahan, Timothy P Birkland, Kate S Smigiel, Tyler C Vandivort, Maryam G Rohani, Anne M Manicone, John K McGuire, Sina A Gharib, William C Parks
Several members of the matrix metalloproteinase (MMP) family control a range of immune processes, such as leukocyte influx and chemokine activity. Stromelysin-2 (MMP10) is expressed by macrophages in numerous tissues after injury; however, little is known of its function. In this study, we report that MMP10 is expressed by macrophages in human lungs from patients with cystic fibrosis and induced in mouse macrophages in response to Pseudomonas aeruginosa infection both in vivo and by isolated resident alveolar and bone marrow-derived macrophages (BMDM)...
August 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Karuna Patil, Lee Ann Campbell, Michael E Rosenfeld, Jisun Paik, Thea Brabb, Kevin D O'brien, Lillian Maggio-Price, Charlie C Hsu
Chlamydia pneumoniae (Cpn), a common respiratory pathogen of humans, is associated with human cardiovascular disease and the acceleration of atherosclerosis in hyperlipidemic animal models. Our laboratory has demonstrated that murine norovirus (MNV), a prevalent infection of laboratory mice, can unpredictably alter atherosclerosis in hyperlipidemic Ldlr(-/-) and ApoE(-/-) mice. Given that MNV has a tropism for macrophages and may exacerbate atherogenesis, we investigated whether coinfection with MNV and Cpn might alter macrophage phenotypes in vitro and atherosclerosis in ApoE(-/-) mice...
2016: Comparative Medicine
Ajay Kumar, Shailendra Giri, Ashok Kumar
The retina is considered to be the most metabolically active tissue in the body. However, the link between energy metabolism and retinal inflammation, as incited by microbial infection such as endophthalmitis remains unexplored. In this study, using a mouse model of Staphylococcus aureus (SA) endophthalmitis, we demonstrate that the activity (phosphorylation) of AMP-activated protein kinase alpha (AMPKα), a cellular energy sensor, and its endogenous substrate; acetyl-CoA carboxylase (ACC) is downregulated in the SA-infected retina...
June 5, 2016: Cellular Microbiology
Tassili A F Weehuizen, Tijmen J Hommes, Jacqueline M Lankelma, Hanna K de Jong, Joris J T H Roelofs, Alex F de Vos, Marco Colonna, Tom van der Poll, W Joost Wiersinga
BACKGROUND: Triggering receptor expressed on myeloid cells (TREM) -1 and TREM-2 are key regulators of the inflammatory response that are involved in the clearance of invading pathogens. Melioidosis, caused by the "Tier 1" biothreat agent Burkholderia pseudomallei, is a common form of community-acquired sepsis in Southeast-Asia. TREM-1 has been suggested as a biomarker for sepsis and melioidosis. We aimed to characterize the expression and function of TREM-1 and TREM-2 in melioidosis. METHODOLOGY/PRINCIPAL FINDINGS: Wild-type, TREM-1/3 (Trem-1/3-/-) and TREM-2 (Trem-2-/-) deficient mice were intranasally infected with live B...
June 2016: PLoS Neglected Tropical Diseases
Karina Schuch, Bettina Wanko, Katharina Ambroz, Alexandra Castelo-Rosa, Verónica Moreno-Viedma, Nicole G Grün, Lukas Leitner, Günther Staffler, Maximilian Zeyda, Thomas M Stulnig
OBJECTIVE: Macrophages are the main drivers of obesity-induced adipose tissue (AT) inflammation that causes insulin resistance. Macrophages polarize toward different inflammatory (M1) or protective (M2) phenotypes. Osteopontin (OPN) is an inflammatory cytokine highly expressed in AT in obesity and known to be involved in chronic inflammatory processes. It was hypothesized that OPN polarizes macrophages into a proinflammatory phenotype. METHODS: AT macrophages (ATMs) of OPN-deficient (Spp1(-/-) ) and wild-type C57BL/6 (WT) mice with obesity and bone marrow-derived macrophages (BMDMs) of Spp1(-/-) and WT mice as well as human monocyte-derived macrophages (MDMs) polarized in the presence of OPN were investigated...
July 2016: Obesity
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