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https://www.readbyqxmd.com/read/28329706/exposure-to-bacterial-cpg-dna-protects-from-airway-allergic-inflammation-by-expanding-regulatory-lung-interstitial-macrophages
#1
Catherine Sabatel, Coraline Radermecker, Laurence Fievez, Genevieve Paulissen, Svetoslav Chakarov, Claudia Fernandes, Sabine Olivier, Marie Toussaint, Dimitri Pirottin, Xue Xiao, Pascale Quatresooz, Jean-Claude Sirard, Didier Cataldo, Laurent Gillet, Hicham Bouabe, Christophe J Desmet, Florent Ginhoux, Thomas Marichal, Fabrice Bureau
Living in a microbe-rich environment reduces the risk of developing asthma. Exposure of humans or mice to unmethylated CpG DNA (CpG) from bacteria reproduces these protective effects, suggesting a major contribution of CpG to microbe-induced asthma resistance. However, how CpG confers protection remains elusive. We found that exposure to CpG expanded regulatory lung interstitial macrophages (IMs) from monocytes infiltrating the lung or mobilized from the spleen. Trafficking of IM precursors to the lung was independent of CCR2, a chemokine receptor required for monocyte mobilization from the bone marrow...
March 21, 2017: Immunity
https://www.readbyqxmd.com/read/28323963/an-antibody-to-notch2-reverses-the-osteopenic-phenotype-of-hajdu-cheney-mutant-male-mice
#2
Ernesto Canalis, Archana Sanjay, Jungeun Yu, Stefano Zanotti
Notch receptors play a central role in skeletal development and bone remodeling. Hajdu Cheney Syndrome (HCS), a disease characterized by osteoporosis and fractures, is associated with gain-of-NOTCH2 function mutations. To study HCS, we created a mouse model harboring a point 6955C>T mutation in the Notch2 locus upstream of the proline (P), glutamic acid (E), serine (S) and threonine (T) domain leading to a Q2319X change at the amino acid level. Notch2Q2319X heterozygous mutants exhibited cancellous and cortical bone osteopenia...
January 31, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323104/cytotoxicity-and-genotoxicity-of-lipid-nanocapsules
#3
Gaël Le Roux, Hélène Moche, Alejandro Nieto, Jean-Pierre Benoit, Fabrice Nesslany, Frédéric Lagarce
Lipid nanocapsules (LNCs) offer a promising method for the entrapment and nanovectorisation of lipophilic molecules. This new type of nanocarrier, formulated according to a solvent-free process and using only regulatory-approved components, exhibits many prerequisites for being well tolerated. Although toxicological reference values have already been obtained in mice, interaction of LNCs at the cell level needs to be elucidated. LNCs, measuring from 27.0±0.1nm (25nm LNCs) and 112.1±1.8nm (100nm LNCs) and with a zeta potential between -38...
March 17, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28323006/the-role-of-sumoylation-in-cerebral-hypoxia-and-ischemia
#4
REVIEW
Myriam Peters, Betty Wielsch, Johannes Boltze
The process of protein modification by adding or detaching small ubiquitin-like modifiers (SUMO) proteins, called SUMOylation, contributes to the regulation of numerous processes in eukaryotic cells. SUMOylation also represents a key response and adaption mechanism to different forms of metabolic stress. The central nervous system (CNS) and neurons in particular are highly susceptible to hypoxic-ischemic stress due to the lack of significant oxygen and energy reserves. SUMOylation is observed in many molecular responses to metabolic stress in the brain, and is therefore supposed to represent an endogenous neuroprotective mechanism...
March 17, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28315683/klotho-ameliorates-cyclosporine-a-induced-nephropathy-via-pdlim2-nf-kb-p65-signaling-pathway
#5
Meihua Jin, Pengfei Lv, Guanyu Chen, Peng Wang, Zhongfu Zuo, Lili Ren, Jing Bi, Chul-Woo Yang, Xifan Mei, Donghe Han
Klotho, an antiaging protein, can extend the lifespan and modulate cellular responses to inflammation and oxidative stress which can ameliorate chronic kidney diseases (CKD). To investigate the molecular mechanism of Klotho on inflammation in cyclosporine A (CsA) induced nephropathy, the mice were transfected with adenovirus mediated Klotho gene and treated with cyclosporine A (CsA; 30 mg/kg/day) for 4 weeks. Also, primary human renal proximal tubule epithelial cells (RPTECs) were treated with soluble Klotho protein and LPS...
March 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28314590/inflammasome-activation-triggers-caspase-1-mediated-cleavage-of-cgas-to-regulate-responses-to-dna-virus-infection
#6
Yutao Wang, Xiaohan Ning, Pengfei Gao, Shuxian Wu, Mengyin Sha, Mengze Lv, Xiang Zhou, Juyi Gao, Run Fang, Guangxun Meng, Xiaodong Su, Zhengfan Jiang
Viral infection triggers host innate immune responses that result in the production of various cytokines including type I interferons (IFN), activation of inflammasomes, and programmed cell death of the infected cells. Tight control of inflammatory cytokine production is crucial for the triggering of an effective immune response that can resolve the infection without causing host pathology. In examining the inflammatory response of Asc(-/-) and Casp1(-/-) macrophages, we found that deficiency in these molecules resulted in increased IFN production upon DNA virus infection, but not RNA virus challenge...
March 21, 2017: Immunity
https://www.readbyqxmd.com/read/28303004/serum-fabp5-concentration-is-a-potential-biomarker-for-residual-risk-of-atherosclerosis-in-relation-to-cholesterol-efflux-from-macrophages
#7
Masato Furuhashi, Masatsune Ogura, Megumi Matsumoto, Satoshi Yuda, Atsuko Muranaka, Mina Kawamukai, Akina Omori, Marenao Tanaka, Norihito Moniwa, Hirofumi Ohnishi, Shigeyuki Saitoh, Mariko Harada-Shiba, Kazuaki Shimamoto, Tetsuji Miura
Cholesterol efflux capacity (CEC) from macrophages, the first step in the reverse cholesterol transport pathway, is inversely associated with residual risk for atherosclerotic cardiovascular disease. Fatty acid-binding protein 4 (FABP4) and FABP5 are expressed in both adipocytes and macrophages and play significant roles in the development of insulin resistance and atherosclerosis. Both FABP4 and FABP5 are secreted from cells, and their circulating levels are associated with insulin resistance and atherosclerosis...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28302726/the-rna-binding-protein-tristetraprolin-ttp-is-a-critical-negative-regulator-of-the-nlrp3-inflammasome
#8
Moritz Haneklaus, John D O'Neil, Andrew R Clark, Seth L Masters, Luke A J O'Neill
The NLRP3 inflammasome is a central regulator of inflammation in many common diseases, including atherosclerosis and Type 2 diabetes, driving the production of pro-inflammatory mediators such as IL-1β and IL-18. Due to its function as an inflammatory gatekeeper, expression and activation of NLRP3 need to be tightly regulated. In this study, we highlight novel post-transcriptional mechanisms that can modulate NLRP3 expression. We have identified the RNA-binding protein Tristetraprolin (TTP) as a negative regulator of NLRP3 in human macrophages...
March 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28301468/recessive-coding-and-regulatory-mutations-in-fblim1-underlie-the-pathogenesis-of-chronic-recurrent-multifocal-osteomyelitis-crmo
#9
Allison J Cox, Benjamin W Darbro, Ronald M Laxer, Gabriel Velez, Xinyu Bing, Alexis L Finer, Albert Erives, Vinit B Mahajan, Alexander G Bassuk, Polly J Ferguson
Chronic recurrent multifocal osteomyelitis (CRMO) is a rare, pediatric, autoinflammatory disease characterized by bone pain due to sterile osteomyelitis, and is often accompanied by psoriasis or inflammatory bowel disease. There are two syndromic forms of CRMO, Majeed syndrome and DIRA, for which the genetic cause is known. However, for the majority of cases of CRMO, the genetic basis is unknown. Via whole-exome sequencing, we detected a homozygous mutation in the filamin-binding domain of FBLIM1 in an affected child with consanguineous parents...
2017: PloS One
https://www.readbyqxmd.com/read/28296821/protease-activated-receptor-1-plays-a-proinflammatory-role-in-colitis-by-promoting-th17-related-immunity
#10
Muhammad A Saeed, Garrett Z Ng, Jan Däbritz, Josef Wagner, Louise Judd, Jia-Xi Han, Poshmaal Dhar, Carl D Kirkwood, Philip Sutton
BACKGROUND: Proteolytic cleavage of protease-activated receptor 1 (PAR1) can result in potent downstream regulatory effects on inflammation. Although PAR1 is expressed throughout the gastrointestinal tract and activating proteases are increased in inflammatory bowel disease, the effect of PAR1 activation on colitis remains poorly understood, and has not previously been studied in pediatric disease. METHODS: Expression of PAR1 and inflammatory cytokines in colonic biopsies from pediatric patients with Crohn's disease exhibiting active moderate to severe colitis was measured by quantitative PCR...
April 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28293730/liver-macrophages-in-healthy-and-diseased-liver
#11
REVIEW
Zeinab Abdullah, Percy A Knolle
Kupffer cells, the largest tissue resident macrophage population, are key for the maintenance of liver integrity and its restoration after injury and infections, as well as the local initiation and resolution of innate and adaptive immunity. These important roles of Kupffer cells were recently identified in healthy and diseased liver revealing diverse functions and phenotypes of hepatic macrophages. High-level phenotypic and genomic analysis revealed that Kupffer cells are not a homogenous population and that the hepatic microenvironment actively shapes both phenotype and function of liver macrophages...
April 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28292326/immune-mediators-in-the-tumor-microenvironment-of-prostate-cancer
#12
REVIEW
Jinlu Dai, Yi Lu, Hernan Roca, Jill M Keller, Jian Zhang, Laurie K McCauley, Evan T Keller
Prostate cancer tissue is composed of both cancer cells and host cells. The milieu of host components that compose the tumor is termed the tumor microenvironment (TME). Host cells can be those derived from the tissue in which the tumor originates (e.g., fibroblasts and endothelial cells) or those recruited, through chemotactic or other factors, to the tumor (e.g., circulating immune cells). Some immune cells are key players in the TME and represent a large proportion of non-tumor cells found within the tumor...
March 14, 2017: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/28289705/als-patients-regulatory-t-lymphocytes-are-dysfunctional-and-correlate-with-disease-progression-rate-and-severity
#13
David R Beers, Weihua Zhao, Jinghong Wang, Xiujun Zhang, Shixiang Wen, Dan Neal, Jason R Thonhoff, Abdullah S Alsuliman, Elizabeth J Shpall, Katy Rezvani, Stanley H Appel
Neuroinflammation is a pathological hallmark of ALS in both transgenic rodent models and patients, and is characterized by proinflammatory T lymphocytes and activated macrophages/microglia. In ALS mouse models, decreased regulatory T lymphocytes (Tregs) exacerbate the neuroinflammatory process, leading to accelerated motoneuron death and shortened survival; passive transfer of Tregs suppresses the neuroinflammation and prolongs survival. Treg numbers and FOXP3 expression are also decreased in rapidly progressing ALS patients...
March 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28289091/membrane-nanoclusters-of-fc%C3%AE-ri-segregate-from-inhibitory-sirp%C3%AE-upon-activation-of-human-macrophages
#14
Filipa B Lopes, Štefan Bálint, Salvatore Valvo, James H Felce, Edith M Hessel, Michael L Dustin, Daniel M Davis
Signal integration between activating Fc receptors and inhibitory signal regulatory protein α (SIRPα) controls macrophage phagocytosis. Here, using dual-color direct stochastic optical reconstruction microscopy, we report that Fcγ receptor I (FcγRI), FcγRII, and SIRPα are not homogeneously distributed at macrophage surfaces but are organized in discrete nanoclusters, with a mean radius of 71 ± 11 nm, 60 ± 6 nm, and 48 ± 3 nm, respectively. Nanoclusters of FcγRI, but not FcγRII, are constitutively associated with nanoclusters of SIRPα, within 62 ± 5 nm, mediated by the actin cytoskeleton...
March 13, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28287634/immune-microenvironment-of-gliomas
#15
Anna Gieryng, Dominika Pszczolkowska, Kacper A Walentynowicz, Wenson D Rajan, Bozena Kaminska
High-grade gliomas are rapidly progressing tumors of the central nervous system (CNS) with a very poor prognosis despite extensive resection combined with radiation and/or chemotherapy. Histopathological and flow cytometry analyses of human and rodent experimental gliomas revealed heterogeneity of a tumor and its niche, composed of reactive astrocytes, endothelial cells, and numerous immune cells. Infiltrating immune cells consist of CNS resident (microglia) and peripheral macrophages, granulocytes, myeloid-derived suppressor cells (MDSCs), and T lymphocytes...
March 13, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28286938/n-acetyl-l-cysteine-controls-osteoclastogenesis-through-regulating-th17-differentiation-and-rankl-in-rheumatoid-arthritis
#16
Hae-Rim Kim, Kyoung-Woon Kim, Bo-Mi Kim, Kyung-Ann Lee, Sang-Heon Lee
Background/Aims: This study aimed to determine the regulatory role of N-acetyl-l-cysteine (NAC), an antioxidant, in interleukin 17 (IL-17)-induced osteoclast differentiation in rheumatoid arthritis (RA). Methods: After RA synovial fibroblasts were stimulated by IL-17, the expression and production of receptor activator of nuclear factor κ-B ligand (RANKL) was determined by real-time polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA). Osteoclastogenesis was also determined after co-cultures of IL-17-stimulated RA synovial fibroblasts, Th17 cells and various concentrations of NAC with monocytes...
March 13, 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/28286378/iron-reduces-m1-macrophage-polarization-in-raw264-7-macrophages-associated-with-inhibition-of-stat1
#17
Zhen-Shun Gan, Qian-Qian Wang, Jia-Hui Li, Xu-Liang Wang, Yi-Zhen Wang, Hua-Hua Du
Iron metabolism in inflammation has been mostly characterized in macrophages exposed to pathogens or inflammatory conditions. The aim of this study is to investigate the cross-regulatory interactions between M1 macrophage polarization and iron metabolism. Firstly, we characterized the transcription of genes related to iron homeostasis in M1 RAW264.7 macrophages stimulated by IFN-γ. The molecular signature of M1 macrophages showed high levels of iron storage (ferritin), a low level of iron export (ferroportin), and changes of iron regulators (hepcidin and transferrin receptors), which favour iron sequestration in the reticuloendothelial system and are benefit for inflammatory disorders...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28286286/cancer-immunotherapy-targeting-the-cd47-sirp%C3%AE-axis
#18
REVIEW
Kipp Weiskopf
The success of cancer immunotherapy has generated tremendous interest in identifying new immunotherapeutic targets. To date, the majority of therapies have focussed on stimulating the adaptive immune system to attack cancer, including agents targeting CTLA-4 and the PD-1/PD-L1 axis. However, macrophages and other myeloid immune cells offer much promise as effectors of cancer immunotherapy. The CD47/signal regulatory protein alpha (SIRPα) axis is a critical regulator of myeloid cell activation and serves a broader role as a myeloid-specific immune checkpoint...
March 9, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28284455/uterine-nk-cells-and-macrophages-in-pregnancy
#19
Marijke M Faas, Paul de Vos
The presence of immune cells in the placental bed is important for both mother and child. Although various immune cells can be found in the placental bed, such as regulatory T cells and dendritic cells, uterine NK cells and macrophages are the most prominent immune cells in the placental bed in early pregnancy. uNK cell and macrophage numbers in the placental bed decrease in the third trimester. These cells seem to be specifically adapted for their function and environment. uNK cells do not show cytotoxic activity, but are producers of cytokines, growth factors and many other factors...
March 2, 2017: Placenta
https://www.readbyqxmd.com/read/28284347/novel-feedback-loop-between-m2-macrophages-microglia-and-regulatory-b-cells-in-estrogen-protected-eae-mice
#20
Gil Benedek, Jun Zhang, Ha Nguyen, Gail Kent, Hilary Seifert, Arthur A Vandenbark, Halina Offner
Immunoregulatory sex hormones, including estrogen and estriol, may prevent relapses in multiple sclerosis during pregnancy. Our previous studies have demonstrated that regulatory B cells are crucial for estrogen-mediated protection against experimental autoimmune encephalomyelitis (EAE). Herein, we demonstrate an estrogen-dependent induction of alternatively activated (M2) macrophages/microglia that results in an increased frequency of regulatory B cells in the spinal cord of estrogen treated mice with EAE...
April 15, 2017: Journal of Neuroimmunology
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