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https://www.readbyqxmd.com/read/28646881/heme-molecule-functions-as-an-endogenous-agonist-of-astrocyte-tlr2-to-contribute-to-secondary-brain-damage-after-intracerebral-hemorrhage
#1
Hyunjung Min, Boomin Choi, Yong Ho Jang, Ik-Hyun Cho, Sung Joong Lee
Toll-like receptor 2 (TLR2) was recently shown to contribute to secondary brain damage after intracerebral hemorrhage (ICH), although the molecular mechanisms of this contribution are elusive. In this study, we tested the hypothesis that hemin functions as a TLR2 endogenous agonist, causing proinflammatory astrocyte activation and secondary brain damage after ICH. Hemin administration to the mouse brain striatum induced ICH injury and neurological deficits, however, the brain injury volume and neurological deficits due to hemin injection were significantly reduced in TLR2 knock-out (KO) mice...
June 24, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28643374/population-pharmacokinetic-and-pharmacodynamic-modeling-of-ly2510924-in-patients-with-advanced-cancer
#2
S Bihorel, E Raddad, J Fiedler-Kelly, J R Stille, J Hing, E Ludwig
The objectives of this study were to characterize the pharmacokinetics (PK) of LY2510924, a potent peptide antagonist of the CXCR4 receptor, after subcutaneous administration in patients with advanced cancer forms and quantify LY2510924 stimulatory effects on the mobilization of cells bearing the cluster of differentiation 34 (CD34) as an indirect reflection of the chemokine C-X-C motif ligand 12/CXCR4 axis inhibition. LY2510924 PK were best characterized by a 2-compartment model with first-order absorption and dose-dependent clearance predicting steady state after three daily doses and little accumulation (accumulation ratio <1...
June 23, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28642703/different-regulation-of-interleukin-1-production-and-activity-in-monocytes-and-macrophages-innate-memory-as-an-endogenous-mechanism-of-il-1-inhibition
#3
Mariusz P Madej, Elfi Töpfer, Diana Boraschi, Paola Italiani
Production and activity of interleukin (IL)-1β are kept under strict control in our body, because of its powerful inflammation-promoting capacity. Control of IL-1β production and activity allows IL-1 to exert its defensive activities without causing extensive tissue damage. Monocytes are the major producers of IL-1β during inflammation, but they are also able to produce significant amounts of IL-1 inhibitors such as IL-1Ra and the soluble form of the decoy receptor IL-1R2, in an auto-regulatory feedback loop...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28642238/ager-deletion-enhances-ischemic-muscle-inflammation-neoangiogenesis-and-blood-flow-recovery-in-diabetic-mice
#4
Raquel Lopez Diez, Xiaoping Shen, Gurdip Daffu, Md Khursheed, Jiyuan Hu, Fei Song, Rosa Rosario, Yunlu Xu, Qing Li, Xiangmei Xi, Yu Shan Zou, Huilin Li, Ann Marie Schmidt, Shi Fang Yan
OBJECTIVE: Diabetic subjects are at higher risk of ischemic peripheral vascular disease. We tested the hypothesis that advanced glycation end products (AGEs) and their receptor (RAGE) block neoangiogenesis and blood flow recovery after hindlimb ischemia induced by femoral artery ligation through modulation of immune/inflammatory mechanisms. APPROACH AND RESULTS: Wild-type mice rendered diabetic with streptozotocin and subjected to unilateral femoral artery ligation displayed increased accumulation and expression of AGEs and RAGE in ischemic muscle...
June 22, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28642092/chemokine-ccl17-is-expressed-by-dendritic-cells-in-the-cns-during-experimental-autoimmune-encephalomyelitis-and-promotes-pathogenesis-of-disease
#5
Christina Ruland, Hannes Renken, Ivan Kuzmanov, Arezoo Fattahi Mehr, Kathrin Schwarte, Manuela Cerina, Alexander Herrmann, David-Marian Otte, Andreas Zimmer, Nicholas Schwab, Sven G Meuth, Volker Arolt, Luisa Klotz, Irmgard Förster, Stefanie Scheu, Judith Alferink
The CC chemokine ligand 17 (CCL17) and its cognate CC chemokine receptor 4 (CCR4) are known to control leukocyte migration, maintenance of TH17 cells, and regulatory T cell (Treg) expansion in vivo. In this study we characterized the expression and functional role of CCL17 in the pathogenesis of experimental autoimmune encephalomyelitis (EAE). Using a CCL17/EGFP reporter mouse model, we could show that CCL17 expression in the CNS can be found in a subset of classical dendritic cells (DCs) that immigrate into the CNS during the effector phase of MOG-induced EAE...
June 19, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28641070/elmo-proteins-transduce-g-protein-coupled-receptor-signal-to-control-reorganization-of-actin-cytoskeleton-in-chemotaxis-of-eukaryotic-cells
#6
Xuehua Xu, Tian Jin
Chemotaxis, which is chemoattractant-guided directional cell migration, plays major roles in recruitment of neutrophils, the metastasis of cancer cells, and the development of the model organism Dictyostelium discoideum. These cells share remarkable similarities in the signaling pathways by which they control chemotaxis. They all use a G protein-coupled receptor (GPCR)-mediated signal transduction pathway to sense the chemotactic gradient to guide cell migration. Diverse chemokines activate Rac through conserved GPCR signaling pathways...
June 22, 2017: Small GTPases
https://www.readbyqxmd.com/read/28639322/tnf-%C3%AE-induced-nod2-and-rip2-contribute-to-the-up-regulation-of-cytokines-induced-by-mdp-in-monocytic-thp-1-cells
#7
Xiaobin Chen, Zhilin Xiao, Xiumei Xie, Xueting Liu, Manli Jiang, Chuang Yuan, Li Yang, Jinyue Hu
Nucleotide-binding oligomerization domain containing 2 (NOD2)-induced signal transduction and cytokine production is regulated by a number of factors. However, the feedback effect of the pro-inflammatory TNF-α on NOD2-induced inflammation is not fully understood. In this study, we found unexpectedly that TNF-α up-regulated NOD2 ligand MDP-induced production of the CXC chemokines, including CXCL1, 2 and 8, and the pro-inflammatory cytokines, including IL-1β, IL-6 and TNF-α, in a dose-dependent manner at both mRNA and protein levels in monocytic THP-1 cells...
June 21, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28638088/chemokine-receptor-cxcr4-regulates-camkii-creb-pathway-in-spinal-neurons-that-underlies-cancer-induced-bone-pain
#8
Xue-Ming Hu, Hui Zhang, Heng Xu, Hai-Long Zhang, Li-Ping Chen, Wen-Qiang Cui, Wei Yang, Wen Shen
We previously demonstrated that the chemokine receptor CXCR4 plays an important role in cancer-induced bone pain by activating spinal neurons and glial cells. However, the specific neuronal mechanism of CXCR4 signaling is not clear. We further report that CXCR4 contributes to the activation of the neuronal CaMKII/CREB pathway in cancer-induced bone pain. We used a tumor cell implantation (TCI) model and observed that CXCR4, p-CaMKII and p-CREB were persistently up-regulated in spinal neurons. CXCR4 also co-expressed with p-CaMKII and p-CREB, and mediated p-CaMKII and p-CREB expression after TCI...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28637878/cd4-t-cell-and-nk-cell-interplay-key-to-regression-of-mhc-class-i-low-tumors-upon-tlr7-8-agonist-therapy
#9
Elien M Doorduijn, Marjolein Sluijter, Daniela C Salvatori, Serenella Silvestri, Saskia Maas, Ramon Arens, Ferry Ossendorp, Sjoerd H van der Burg, Thorbald van Hall
One of the next challenges in cancer immunotherapy is the resistance of tumors to T cell-based treatments through loss of MHC class I. Here, we show that under these circumstances, the Toll-like receptor (TLR)-7/8 ligand imiquimod, but not the TLR3 ligand poly I:C or TLR9 ligand CpG, mediated an effective antitumor response. The rejection of these immune-escaped cancers was mediated by NK cells and CD4(+) T cells, whereas activated CD8(+) T cells were dispensable. Application of the innate immune stimulator at a distant site activated NK cells and thereby elicited tumor-specific T-cell responses in tumor-bearing mice...
June 21, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28637505/human-lung-and-monocyte-derived-macrophages-differ-with-regard-to-the-effects-of-%C3%AE-2-adrenoceptor-agonists-on-cytokine-release
#10
Tatiana Victoni, Hélène Salvator, Charlotte Abrial, Marion Brollo, Luis Cristovão Sobrino Porto, Vincent Lagente, Emmanuel Naline, Stanislas Grassin-Delyle, Philippe Devillier
BACKGROUND: β2-adrenoceptor agonists have been shown to reduce the lipopolysaccharide (LPS)-induced cytokine release by human monocyte-derived macrophages (MDMs). We compare the expression of β2-adrenoceptors and the inhibitory effect of formoterol and salmeterol on the LPS-induced release of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and a range of chemokines (CCL2, 3, 4, and IL-8) by human lung macrophages (LMs) and MDMs. METHODS: LMs were isolated from patients undergoing resection and MDMs were obtained from blood monocytes in the presence of GM-CSF...
June 21, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28637178/the-at04a-vaccine-against-proprotein-convertase-subtilisin-kexin-type-9-reduces-total-cholesterol-vascular-inflammation-and-atherosclerosis-in-apoe-3leiden-cetp-mice
#11
Christine Landlinger, Marianne G Pouwer, Claudia Juno, José W A van der Hoorn, Elsbet J Pieterman, J Wouter Jukema, Guenther Staffler, Hans M G Princen, Gergana Galabova
Aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising therapeutic target for the treatment of hypercholesterolaemia and atherosclerosis. PCSK9 binds to the low density lipoprotein receptor and enhances its degradation, which leads to the reduced clearance of low density lipoprotein cholesterol (LDLc) and a higher risk of atherosclerosis. In this study, the AT04A anti-PCSK9 vaccine was evaluated for its therapeutic potential in ameliorating or even preventing coronary heart disease in the atherogenic APOE*3Leiden...
June 19, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28637014/a-combination-of-valproic-acid-sodium-salt-chir99021-e-616452-tranylcypromine-and-3-deazaneplanocin-a-causes-stem-cell-like-characteristics-in-cancer-cells
#12
Shuang Sha, Yuanfen Zhai, Chengzhao Lin, Heyong Wang, Qing Chang, Shuang Song, Mingqiang Ren, Gentao Liu
Many studies are based on the hypothesis that recurrence and drug resistance in lung carcinoma are due to a subpopulation of cancer stem-like cells (CSLCs) in solid tumors. Therefore it is crucial to screen for and recognize lung CSLCs. In this study, we stimulated non-small cell lung cancer (NSCLC) A549 cells to display stem cell-like characteristics using a combination of five small molecule compounds. The putative A549 stem cells activated an important CSLC marker, CD133 protein, as well multiple CSLC-related genes including ATP-binding cassette transporter G2 (ABCG2), C-X-C chemokine receptor type 4 (CXCR4), NESTIN, and BMI1...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28637005/cxcl13-is-androgen-responsive-and-involved-in-androgen-induced-prostate-cancer-cell-migration-and-invasion
#13
Long Fan, Qingyi Zhu, Li Liu, Cuicui Zhu, Haojie Huang, Shan Lu, Ping Liu
Androgen receptor (AR) is a key transcription factor playing a critical role in prostate cancer (PCa) initiation and progression. However, the molecular mechanisms of AR action in prostate cancer are not very clear. CXCL13, known as B cell attracting chemokine1 (BCA-1), is a member of CXC chemokine family and relevant to cancer metastasis. This study shows that CXCL13 is an androgen-responsive gene and involved in AR-induced PCa cell migration and invasion. In clinical specimens, expression of CXCL13 in PCa tissues is markedly higher than that in adjacent normal tissues...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636951/structure-of-cc-chemokine-receptor-5-with-a-potent-chemokine-antagonist-reveals-mechanisms-of-chemokine-recognition-and-molecular-mimicry-by-hiv
#14
Yi Zheng, Gye Won Han, Ruben Abagyan, Beili Wu, Raymond C Stevens, Vadim Cherezov, Irina Kufareva, Tracy M Handel
CCR5 is the primary chemokine receptor utilized by HIV to infect leukocytes, whereas CCR5 ligands inhibit infection by blocking CCR5 engagement with HIV gp120. To guide the design of improved therapeutics, we solved the structure of CCR5 in complex with chemokine antagonist [5P7]CCL5. Several structural features appeared to contribute to the anti-HIV potency of [5P7]CCL5, including the distinct chemokine orientation relative to the receptor, the near-complete occupancy of the receptor binding pocket, the dense network of intermolecular hydrogen bonds, and the similarity of binding determinants with the FDA-approved HIV inhibitor Maraviroc...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28635072/plgf-enhances-tlr-dependent-inflammatory-responses-in-human-mononuclear-phagocytes
#15
Laura F Newell, Shernan G Holtan, Jane E Yates, Leonardo Pereira, Jeffrey W Tyner, Irina Burd, Grover C Bagby
PROBLEM: Levels of placental growth factor (PlGF) peak during third trimester of pregnancy, a time when women are at increased risk of virus-induced morbidity. We hypothesized PlGF might contribute to an exaggerated inflammatory response to Toll-like receptor (TLR) activation. METHOD OF STUDY: Primary human adult and cord blood CD14(+) cells were cultured in the presence of TLR ligands and/or PlGF. RESULTS: PlGF significantly enhanced the magnitude and duration of TNF messenger RNA and protein production by TLR-7/8-activated monocytes, and increased subsequent production of TNF-independent inflammatory cytokines...
June 20, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28634370/microbial-antigens-stimulate-metalloprotease-7-secretion-in-human-b-lymphocytes-using-mtor-dependent-and-independent-pathways
#16
Mohamed F Ali, Harika Dasari, Virginia P Van Keulen, Divi Cornec, George Vasmatzis, Tobias Peikert, Eva M Carmona
Metalloproteinases (MMPs) contribute to tissue remodeling and acute inflammation not only by degrading extracellular matrix proteins but also by controlling the influx of chemokines through the regulation and shedding of syndecans. B-lymphocytes, in addition to their well-known function as antibody producing cells, participate in the innate immune response by secreting inflammatory cytokines and chemokines. However, there is little information about the role of B-lymphocytes in the regulation of MMPs; consequently, herein we investigated whether activated human circulating B-lymphocytes contributed to the secretion of MMPs...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634034/absence-of-%C3%AE-chain-in-keratinocytes-alters-chemokine-secretion-resulting-in-reduced-immune-cell-recruitment
#17
Karolin Nowak, Daniela Linzner, Adrian J Thrasher, Paul F Lambert, Wei Li Di, Siobhan O Burns
Loss of function mutations in the common gamma (γc) chain cytokine receptor subunit give rise to severe combined immunodeficiency (SCID) characterised by lack of T and natural killer cells and infant death from infection. Haematopoietic stem cell transplantation or gene therapy offer cure but despite successful replacement of lymphoid immune lineages a long-term risk of severe cutaneous human papilloma virus (HPV) infections persists, possibly related to persistent γc-deficiency in other cell types. Here we demonstrate that keratinocytes, the only cell type directly infected by HPV, express functional γc and its co-receptors...
June 17, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28631842/uk-consensus-statement-on-the-use-of-plerixafor-to-facilitate-autologous-peripheral-blood-stem-cell-collection-to-support-high-dose-chemoradiotherapy-for-patients-with-malignancy
#18
Kenneth W Douglas, Maria Gilleece, Patrick Hayden, Hannah Hunter, Peter R E Johnson, Charlotte Kallmeyer, Ram K Malladi, Shankara Paneesha, Rachel Pawson, Michael Quinn, Kavita Raj, Deborah Richardson, Stephen Robinson, Nigel Russell, John Snowden, Anna Sureda, Eleni Tholouli, Kirsty Thomson, Mike Watts, Keith M Wilson
Plerixafor is a CXC chemokine receptor (CXCR4) antagonist that mobilizes stem cells in the peripheral blood. It is indicated (in combination with granulocyte-colony stimulating factor [G-CSF]) to enhance the harvest of adequate quantities of cluster differentiation (CD) 34+ cells for autologous transplantation in patients with lymphoma or multiple myeloma whose cells mobilize poorly. Strategies for use include delayed re-mobilization after a failed mobilization attempt with G-CSF, and rescue or pre-emptive mobilization in patients in whom mobilization with G-CSF is likely to fail...
June 20, 2017: Journal of Clinical Apheresis
https://www.readbyqxmd.com/read/28630529/effect-of-cyto-chemokine-degradation-in-effective-intercellular-communication-distances
#19
V K Gupta
Many complex biological processes such as cell differentiation, cell proliferation, and cell motility are governed by cell signaling. This mode of intercellular communication is of paramount importance for tissue function and ultimately for entire organism. In intercellular communication cells secrete signaling molecules such as cyto/chemokines which diffuse through the surrounding medium and eventually bind to receptors on other cells whereby the signal transduction is completed. An accurate estimation of the effective communication distances and the time scale on which signaling takes place are important for the interpretation of cell and organ physiology and ultimately in the effective and efficient chemotactically driven tissue engineering...
February 15, 2017: Physica A
https://www.readbyqxmd.com/read/28630102/the-phenotype-and-function-of-preterm-infant-monocytes-implications-for-susceptibility-to-infection
#20
REVIEW
Emma de Jong, Tobias Strunk, David Burgner, Pascal M Lavoie, Andrew Currie
The extreme vulnerability of preterm infants to invasive microbial infections has been attributed to "immature" innate immune defenses. Monocytes are important innate immune sentinel cells critical in the defense against infection in blood. They achieve this via diverse mechanisms that include pathogen recognition receptor- and inflammasome-mediated detection of microbes, migration into infected tissues, and differentiation into Mϕs and dendritic cells, initiation of the inflammatory cascade by free radicals and cytokine/chemokine production, pathogen clearance by phagocytosis and intracellular killing, and the removal of apoptotic cells...
June 19, 2017: Journal of Leukocyte Biology
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