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https://www.readbyqxmd.com/read/28323919/steroids-regulate-cxcl4-in-the-human-endometrium-during-menstruation-to-enable-efficient-endometrial-repair
#1
J A Maybin, U Thiruchelvam, M Madhra, Ptk Saunders, Hod Critchley
Context: Repair of the endometrial surface at menstruation must be efficient to minimize blood loss and optimize reproductive function. The mechanism and regulation of endometrial repair remain undefined. Objective: To determine the presence/regulation of CXCL4 in the human endometrium, as a putative repair factor at menses. Patients/Setting: Endometrium was collected throughout the menstrual cycle from healthy women attending the gynecology department...
February 27, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28319310/cxcl4-is-a-novel-nickel-binding-protein-and-augments-nickel-allergy
#2
Toshinobu Kuroishi, Kanan Bando, Yukinori Tanaka, Kaori Shishido, Masayuki Kinbara, Tomohisa Ogawa, Koji Muramoto, Yasuo Endo, Shunji Sugawara
BACKGROUND: Nickel (Ni) is the most frequent metal allergen and induces a TH1 -dependent type-IV allergy. Although Ni(2+) is considered to bind to endogenous proteins, it currently remains unclear whether these Ni-binding proteins are involved in Ni allergy in vivo. We previously reported the adjuvant effects of lipopolysaccharide (LPS) in a Ni allergy mouse model. Since LPS induces a number of inflammatory mediators, we hypothesized that Ni-binding protein(s) are also induced by LPS...
March 20, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28298564/proteomic-analysis-of-sera-from-individuals-with-diffuse-cutaneous-systemic-sclerosis-reveals-a-multianalyte-signature-associated-with-clinical-improvement-during-imatinib-mesylate-treatment
#3
D James Haddon, Hannah E Wand, Justin A Jarrell, Robert F Spiera, Paul J Utz, Jessica K Gordon, Lorinda S Chung
OBJECTIVE: Imatinib has been investigated for the treatment of systemic sclerosis (SSc) because of its ability to inhibit the platelet-derived growth factor receptor and transforming growth factor-β signaling pathways, which have been implicated in SSc pathogenesis. In a 12-month open-label clinical trial assessing the safety and efficacy of imatinib in the treatment of diffuse cutaneous SSc (dcSSc), significant improvements in skin thickening were observed. Here, we report our analysis of sera collected during the clinical trial...
March 15, 2017: Journal of Rheumatology
https://www.readbyqxmd.com/read/28187313/il-20-contributes-to-low-grade-inflammation-and-weight-gain-in-the-psammomys-obesus
#4
Helena Cucak, Lise Høj Thomsen, Alexander Rosendahl
The metabolic syndrome has been demonstrated in gene deficient animals, e.g. db/db mice, to include a systemic inflammation leading to insulin resistance, obesity and type 2 diabetes (T2D). To determine the importance of inflammation in obesity and diabetes, in a normal non-genetically modified species, an intervention study with neutralizing anti-IL-20 antibodies was conducted in the spontaneous T2D model Psammomys obesus. All IL-20 receptor chains were expressed on protein level in the Psammomys obesus. Neutralization of IL-20 did not modulate blood glucose, HbA1c, insulin levels or lymphocyte numbers after five weeks treatment although a trend to reduced weight gain rate was observed upon anti-IL-20 treatment...
February 7, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28120850/critical-role-of-cxcl4-in-the-lung-pathogenesis-of-influenza-h1n1-respiratory-infection
#5
L Guo, K Feng, Y C Wang, J J Mei, R T Ning, H W Zheng, J J Wang, G S Worthen, X Wang, J Song, Q H Li, L D Liu
Annual epidemics and unexpected pandemics of influenza are threats to human health. Lung immune and inflammatory responses, such as those induced by respiratory infection influenza virus, determine the outcome of pulmonary pathogenesis. Platelet-derived chemokine (C-X-C motif) ligand 4 (CXCL4) has an immunoregulatory role in inflammatory diseases. Here we show that CXCL4 is associated with pulmonary influenza infection and has a critical role in protecting mice from fatal H1N1 virus respiratory infection. CXCL4 knockout resulted in diminished viral clearance from the lung and decreased lung inflammation during early infection but more severe lung pathology relative to wild-type mice during late infection...
January 25, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28038680/changes-in-plasma-cxcl4-levels-are-associated-with-improvements-in-lung-function-in-patients-receiving-immunosuppressive-therapy-for-systemic-sclerosis-related-interstitial-lung-disease
#6
Elizabeth R Volkmann, Donald P Tashkin, Michael D Roth, Philip J Clements, Dinesh Khanna, Daniel E Furst, Maureen Mayes, Julio Charles, Chi-Hong Tseng, Robert M Elashoff, Shervin Assassi
BACKGROUND: Increased circulatory levels of the chemokine CXCL4 have been associated with the presence of interstitial lung disease (ILD) in an observational study of patients with systemic sclerosis (SSc). The purpose of the present study was to evaluate the relationship between baseline CXCL4 level and extent of ILD in the context of a randomized controlled trial and to determine whether changes in CXCL4 levels in response to immunosuppression are associated with future progression of SSc-ILD...
December 30, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28013186/ponciretin-attenuates-ethanol-induced-gastric-damage-in-mice-by-inhibiting-inflammatory-responses
#7
Geum-Dan Kang, Dong-Hyun Kim
BACKGROUND: Poncirin (PO) and isosakuranetin (or ponciretin [PT]) are compounds found in fruits of the genus Citrus. They are frequently used in traditional Chinese medicine for the treatment of inflammation and asthma. Therefore, we examined their anti-gastritis effects in vitro and in vivo. METHODS: The anti-inflammatory effects of PO and PT were examined using ethanol- or LPS-stimulated KATO III cells. Gastritis was induced in ICR mice via intragastric injection of absolute ethanol...
February 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/27829148/pf4-promotes-platelet-production-and-lung-cancer-growth
#8
Ferdinando Pucci, Steffen Rickelt, Andita P Newton, Christopher Garris, Ernesto Nunes, Charles Evavold, Christina Pfirschke, Camilla Engblom, Mari Mino-Kenudson, Richard O Hynes, Ralph Weissleder, Mikael J Pittet
Co-option of host components by solid tumors facilitates cancer progression and can occur in both local tumor microenvironments and remote locations. At present, the signals involved in long-distance communication remain insufficiently understood. Here, we identify platelet factor 4 (PF4, CXCL4) as an endocrine factor whose overexpression in tumors correlates with decreased overall patient survival. Furthermore, engineered PF4 over-production in a Kras-driven lung adenocarcinoma genetic mouse model expanded megakaryopoiesis in bone marrow, augmented platelet accumulation in lungs, and accelerated de novo adenocarcinogenesis...
November 8, 2016: Cell Reports
https://www.readbyqxmd.com/read/27828999/cxcl4-and-cxcl4l1-differentially-affect-monocyte-survival-and-dendritic-cell-differentiation-and-phagocytosis
#9
Mieke Gouwy, Pieter Ruytinx, Egle Radice, Federico Claudi, Katrien Van Raemdonck, Raffaella Bonecchi, Massimo Locati, Sofie Struyf
Upon inflammation, circulating monocytes leave the bloodstream and migrate into the tissues, where they differentiate after exposure to various growth factors, cytokines or infectious agents. The best defined macrophage polarization types are M1 and M2. However, the platelet-derived CXC chemokine CXCL4 induces the polarization of macrophages into a unique phenotype. In this study, we compared the effect of CXCL4 and its variant CXCL4L1 on the differentiation of monocytes into macrophages and into immature monocyte-derived dendritic cells (iMDDC)...
2016: PloS One
https://www.readbyqxmd.com/read/27808577/topoisomerase-i-peptide-loaded-dendritic-cells-induce-autoantibody-response-as-well-as-skin-and-lung-fibrosis
#10
Heena Mehta, Philippe-Olivier Goulet, Vinh Nguyen, Gemma Pérez, Martial Koenig, Jean-Luc Senécal, Marika Sarfati
DNA Topoisomerase I (TopoI) is a candidate autoantigen for diffuse cutaneous systemic sclerosis (dcSSc) associated with fatal lung disease. Dendritic cells (DCs) contribute to bleomycin-induced lung fibrosis. However, the possibility that TopoI-loaded DCs are involved in the initiation and/or perpetuation of dcSSc has not been explored. Here, we show that immunization with TopoI peptide-loaded DCs induces anti-TopoI autoantibody response and long-term fibrosis. Mice were repeatedly immunized with unpulsed DCs or DCs loaded with either TOPOIA or TOPOIB peptides, selected from different regions of TopoI...
November 3, 2016: Autoimmunity
https://www.readbyqxmd.com/read/27755915/platelet-specific-chemokines-contribute-to-the-pathogenesis-of-acute-lung-injury
#11
Khalil Bdeir, Kandace Gollomp, Marta Stasiak, Junjie Mei, Izabela Papiewska-Pajak, Guohua Zhao, G Scott Worthen, Douglas B Cines, Mortimer Poncz, M Anna Kowalska
Platelets and neutrophils contribute to the development of acute lung injury (ALI). However, the mechanism by which platelets make this contribution is incompletely understood. We investigated whether the two most abundant platelet chemokines, CXCL7, which induces neutrophil chemotaxis and activation, and CXCL4, which does neither, mediate ALI through complementary pathogenic pathways. To examine the role of platelet-derived chemokines in the pathogenesis of ALI using Cxcl7(-/-) and Cxcl4(-/-) knockout mice and mice that express human CXCL7 or CXCL4, we measured levels of chemokines in these mice...
February 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27683760/pathophysiological-relevance-of-macrophage-subsets-in-atherogenesis
#12
Luca Liberale, Franco Dallegri, Fabrizio Montecucco, Federico Carbone
Macrophages are highly heterogeneous and plastic cells. They were shown to play a critical role in all stages of atherogenesis, from the initiation to the necrotic core formation and plaque rupture. Lesional macrophages primarily derive from blood monocyte, but local macrophage proliferation as well as differentiation from smooth muscle cells have also been described. Within atherosclerotic plaques, macrophages rapidly respond to changes in the microenvironment, shifting between pro- (M1) or anti-inflammatory (M2) functional phenotypes...
September 29, 2016: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/27659014/stromal-ets2-regulates-chemokine-production-and-immune-cell-recruitment-during-acinar-to-ductal-metaplasia
#13
Jason R Pitarresi, Xin Liu, Sudarshana M Sharma, Maria C Cuitiño, Raleigh D Kladney, Thomas A Mace, Sydney Donohue, Sunayana G Nayak, Chunjing Qu, James Lee, Sarah A Woelke, Stefan Trela, Kyle LaPak, Lianbo Yu, Joseph McElroy, Thomas J Rosol, Reena Shakya, Thomas Ludwig, Gregory B Lesinski, Soledad A Fernandez, Stephen F Konieczny, Gustavo Leone, Jinghai Wu, Michael C Ostrowski
Preclinical studies have suggested that the pancreatic tumor microenvironment both inhibits and promotes tumor development and growth. Here we establish the role of stromal fibroblasts during acinar-to-ductal metaplasia (ADM), an initiating event in pancreatic cancer formation. The transcription factor V-Ets avian erythroblastosis virus E26 oncogene homolog 2 (ETS2) was elevated in smooth muscle actin-positive fibroblasts in the stroma of pancreatic ductal adenocarcinoma (PDAC) patient tissue samples relative to normal pancreatic controls...
September 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27650429/cxcl4-in-undifferentiated-connective-tissue-disease-at-risk-for-systemic-sclerosis-ssc-previously-referred-to-as-very-early-ssc
#14
Gabriele Valentini, Antonella Riccardi, Serena Vettori, Rosaria Irace, Michele Iudici, Salvatore Tolone, Ludovico Docimo, Marialuisa Bocchino, Alessandro Sanduzzi, Domenico Cozzolino
The aim of the study was to evaluate CXCL4 levels in undifferentiated connective tissue disease at risk for SSc (UCTD-SSc-risk) and confirm its increase and investigate its prognostic value. Serum CXCL4 levels were measured in 45 patients and 24 controls. CXCL4 was significantly higher in UCTD-SSc-risk patients than in controls. It resulted higher in patients with a shorter disease duration and in those lacking capillaroscopic alterations. We confirm that CXCL4 levels are increased in UCTD-risk-SSc patients...
September 20, 2016: Clinical and Experimental Medicine
https://www.readbyqxmd.com/read/27634764/dual-roles-for-cxcl4-chemokines-and-cxcr3-in-angiogenesis-and-invasion-of-pancreatic-cancer
#15
Cathy Quemener, Jessica Baud, Kevin Boyé, Alexandre Dubrac, Clotilde Billottet, Fabienne Soulet, Florence Darlot, Laurent Dumartin, Marie Sire, Renaud Grepin, Thomas Daubon, Fabienne Rayne, Harald Wodrich, Anne Couvelard, Raphael Pineau, Martin Schilling, Vincent Castronovo, Shih-Che Sue, Kim Clarke, Abderrahim Lomri, Abdel-Majid Khatib, Martin Hagedorn, Hervé Prats, Andreas Bikfalvi
The CXCL4 paralog CXCL4L1 is a less studied chemokine that has been suggested to exert an antiangiogenic function. However, CXCL4L1 is also expressed in patient tumors, tumor cell lines, and murine xenografts, prompting a more detailed analysis of its role in cancer pathogenesis. We used genetic and antibody-based approaches to attenuate CXCL4L1 in models of pancreatic ductal adenocarcinoma (PDAC). Mechanisms of expression were assessed in cell coculture experiments, murine, and avian xenotransplants, including through an evaluation of CpG methylation and mutation of critical CpG residues...
November 15, 2016: Cancer Research
https://www.readbyqxmd.com/read/27633389/mkey-a-peptide-inhibitor-of-cxcl4-ccl5-heterodimer-formation-protects-against-stroke-in-mice
#16
Yifang Fan, Xiaoxing Xiong, Yongming Zhang, Dongmei Yan, Zhihong Jian, Baohui Xu, Heng Zhao
BACKGROUND: MKEY, a synthetic cyclic peptide inhibitor of CXCL4-CCL5 heterodimer formation, has been shown to protect against atherosclerosis and aortic aneurysm formation by mediating inflammation, but whether it modulates neuroinflammation and brain injury has not been studied. We therefore studied the role of MKEY in stroke-induced brain injury in mice. METHODS AND RESULTS: MKEY was injected into mice after stroke with 60 minutes of middle cerebral artery occlusion...
September 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27562035/serum-cxcl4-increase-in-primary-sj%C3%A3-gren-s-syndrome-characterizes-patients-with-microvascular-involvement-and-reduced-salivary-gland-infiltration-and-lymph-node-involvement
#17
Serena Vettori, Rosaria Irace, Antonella Riccardi, Daniela Iacono, Luciana Pellecchia, Lucia Vicedomini, Gabriele Valentini
CXCL4 is an antiangiogenic and immunomodulatory chemokine. We aimed to investigate serum levels of CXCL4 in primary Sjögren's syndrome (pSS), looking for associations with disease features. Thirty-nine consecutive pSS patients underwent clinical-serological assessment and nailfold videocapillaroscopy (NVC). Thirty-six patients and 30 controls affected by osteoarthritis were also investigated for serum levels of CXCL4 and soluble E-selectin (sE-selectin). CXCL4 was higher in pSS patients than in controls (1...
October 2016: Clinical Rheumatology
https://www.readbyqxmd.com/read/27546737/irisolidone-attenuates-ethanol-induced-gastric-injury-in-mice-by-inhibiting-the-infiltration-of-neutrophils
#18
Geum-Dan Kang, Sang-Yoon Lee, Se-Eun Jang, Myung Joo Han, Dong-Hyun Kim
SCOPE: This study was designed to determine whether irisolidone and its glycoside kakkalide, which are the major constituents of the flower of Pueraria lobata (Kudzu) can attenuate ethanol-induced gastritic injury in mice. METHODS AND RESULTS: Irisolidone and kakkalide inhibited IL-8 secretion and NF-κB activation in lipopolysaccharide-stimulated KATO III cells. Therefore, we investigated their protective effects against ethanol-induced gastric injury in mice. Pretreatment with kakkalide or irisolidone decreased the area of hemorrhagic ulcerative lesions caused by ethanol and suppressed stomach myeloperoxidase activity, CXCL4 secretion, and NF-κB activation...
October 5, 2016: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/27512119/cxc-chemokine-receptor-3-alternative-splice-variants-selectively-activate-different-signaling-pathways
#19
Yamina A Berchiche, Thomas P Sakmar
The G protein-coupled receptor (GPCR) C-X-C chemokine receptor 3 (CXCR3) is a potential drug target that mediates signaling involved in cancer metastasis and inflammatory diseases. The CXCR3 primary transcript has three potential alternative splice variants and cell-type specific expression results in receptor variants that are believed to have different functional characteristics. However, the molecular pharmacology of ligand binding to CXCR3 alternative splice variants and their downstream signaling pathways remain poorly explored...
October 2016: Molecular Pharmacology
https://www.readbyqxmd.com/read/27468759/infiltration-of-myeloid-cells-in-the-pregnant-uterus-is-affected-by-heme-oxygenase-1
#20
Hui Zhao, Flora Kalish, Ronald J Wong, David K Stevenson
Infiltrating myeloid cells in pregnant uteri play critical roles in the establishment of the placenta and maintenance of normal pregnancies. Their recruitment and proliferation are primarily mediated by the interactions of cytokines and chemokines secreted locally with their corresponding receptors. Heme oxygenase-1 (HO-1) has various physiologic properties that contribute to placental vascular development, with deficiencies in HO-1 associated with pregnancy disorders. Here, we investigated the effect of HO-1 on myeloid cell infiltration into pregnant uteri using a partial HO-1-deficient (Het, HO-1(+/-)) mouse model...
January 2017: Journal of Leukocyte Biology
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