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chemokine receptor

David F Woodward, Jenny W Wang, Ming Ni, Alex Bauer, Jose L Martos, Robert W Carling, Neil J Poloso
The purpose of these studies was to test the hypothesis that a selected polypharmacological approach for treating the prostanoid-mediated component of inflammatory diseases would produce a therapeutic effect superior to global inhibition of prostaglandin (PG) biosynthesis by aspirin-like drugs. The compound studied was AGN 211377, which had been previously shown to produce a superior effect on cytokine release from human macrophages compared with cyclooxygenase (COX) inhibitors. AGN 211377 antagonizes prostanoid prostaglandin D2 (DP)1, DP2, prostaglandin E2 (EP)1, EP4, prostaglandin F2α, and thromboxane A2 receptors but not anti-inflammatory EP2, prostaglandin I2, or EP3 receptors...
October 21, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Kensuke Yamamura, Yoshifumi Baba, Shigeki Nakagawa, Kosuke Mima, Keisuke Miyake, Kenichi Nakamura, Hiroshi Sawayama, Koichi Kinoshita, Takatsugu Ishimoto, Masaaki Iwatsuki, Yasuo Sakamoto, Yoichi Yamashita, Naoya Yoshida, Masayuki Watanabe, Hideo Baba
PURPOSE: Fusobacterium nucleatum (F. nucleatum) is a component of the human microbiome that primarily inhabits the oral cavity. It causes periodontal disease and has also been implicated in the development of human cancers. Although there are several reports of the relationship between F. nucleatum and the clinical outcome in human cancers, its prognostic significance in esophageal cancer remains unclear. EXPERIMENTAL DESIGN: We quantified F. nucleatum DNA in 325 resected esophageal cancer specimens by qPCR...
October 21, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Tan A Nguyen, Ken C Pang, Seth L Masters
An effective innate immune response relies on the detection of pathogen associated molecular patterns (PAMPs) by various host pattern recognition receptors (PRRs) that result in the production of pro-inflammatory cytokines and chemokines. Viruses and bacteria have co-evolved with the immune system and developed multiple strategies to usurp or circumvent host machinery and blunt the innate immune response in infected cells. Recently, it has become apparent that infected or dying cells can transmit PAMPs and host PRR signalling proteins to uninfected bystander cells to thereby bypass pathogen evasion strategies, and potentiate innate immune signalling...
October 18, 2016: Molecular Immunology
K Kajikhina, M Tsuneto, F Melchers
Early in embryonic development of mice, from day 12.5 after conception, myeloid-lymphoid bipotent progenitors, expressing receptors both for IL7 and CSF-1, migrate from embryonic blood into developing fetal liver. These progenitors also express multiple chemokine receptors, i.e., CCR7, CXCR3, CXCR4, and CXCR5, all on one cell. Their migration through LYVE-1+ vascular endothelium is guided by CCR7, recognizing the chemokine CCL19, and by CXCR3, recognizing CXCL10/11, chemokines which are both produced by the endothelium...
2016: Advances in Immunology
Massimo Nabissi, Maria Beatrice Morelli, Massimo Offidani, Consuelo Amantini, Silvia Gentili, Alessandra Soriani, Claudio Cardinali, Pietro Leoni, Giorgio Santoni
Several studies showed a potential anti-tumor role for cannabinoids, by modulating cell signaling pathways involved in cancer cell proliferation, chemo-resistance and migration. Cannabidiol (CBD) was previously noted in multiple myeloma (MM), both alone and in synergy with the proteasome inhibitor bortezomib, to induce cell death. In other type of human cancers, the combination of CBD with Δ9-tetrahydrocannabinol (THC) was found to act synergistically with other chemotherapeutic drugs suggesting their use in combination therapy...
October 18, 2016: Oncotarget
Katrin Feldbauer, Jan Schlegel, Juliane Weissbecker, Frank Sauer, Phillip G Wood, Ernst Bamberg, Ulrich Terpitz
An optochemokine tandem was developed to control the release of calcium from endosomes into the cytosol by light and to analyze the internalization kinetics of G-protein coupled receptors (GPCRs) by electrophysiology. A previously constructed rhodopsin tandem was re-engineered to combine the light-gated Ca2+-permeable cation channel Channelrhodopsin-2(L132C), CatCh, with the chemokine receptor CXCR4 in a functional tandem protein tCXCR4/CatCh. The GPCR was used as a shuttle protein to displace CatCh from the plasma membrane into intracellular areas...
2016: PloS One
Kai Sheng, Jiahuan Lu
Quinones that exist in ambient particulate matter (PM) are hypothesized to be associated with adverse health effects through the generation of reactive oxygen species (ROS). However, the impacts of the quinones on the inflammatory processes have yet to be clearly understood. In this study, we examined the oxidative potentials and biological effects of typical airborne quinones in the human lung epithelial A549 cells. Significant change of redox status, loss of mitochondrial membrane potentials (△Ψ) and increase of superoxide dismutase (SOD) activity were induced by exposure to quinones...
October 21, 2016: Journal of Environmental Science and Health. Part A, Toxic/hazardous Substances & Environmental Engineering
Mengjie Lu, Beili Wu
G protein-coupled receptors (GPCRs) comprise the largest membrane protein family. These receptors sense a variety of signaling molecules, activate multiple intracellular signal pathways, and act as the targets of over 40% of marketed drugs. Recent progress on GPCR structural studies provides invaluable insights into the structure-function relationship of the GPCR superfamily, deepening our understanding about the molecular mechanisms of GPCR signal transduction. Here, we review recent breakthroughs on GPCR structure determination and the structural features of GPCRs, and take the structures of chemokine receptor CCR5 and purinergic receptors P2Y1 R and P2Y12 R as examples to discuss the importance of GPCR structures on functional studies and drug discovery...
October 20, 2016: IUBMB Life
Joern Pezoldt, Jochen Huehn
Upon differentiation, T cells acquire tissue-specific homing properties allowing efficient targeting of effector T cells into distinct inflamed organs. Priming of T cells within skin-draining, peripheral lymph nodes (pLNs) leads to the expression of E- and P-selectin ligands, which facilitate migration into inflamed skin, whereas activation within gut-draining, mesenteric LNs (mLNs) results in induction of chemokine receptor CCR9 and integrin α4β7, both required for migration of effector T cells into mucosal tissues...
September 29, 2016: European Journal of Microbiology & Immunology
Tobias Wiedemann, Stefan Hofbaur, Eva Loell, Gabriele Rieder
Interleukin-8 (IL-8) is a potent neutrophil-activating chemokine which triggers the infiltration and migration of neutrophils into areas of bacterial infection. Helicobacter pylori-infected patient studies as well as animal models have revealed that H. pylori type I strains carrying an intact cytotoxin-associated gene pathogenicity island (cag-PAI) with a functional type IV secretion system (T4SS) induce IL-8 expression and secretion in gastric mucosa. This gastric mucosal IL-8 expression correlates with severe histological changes due to H...
September 29, 2016: European Journal of Microbiology & Immunology
Giovanni Bernardini, Fabrizio Antonangeli, Valentina Bonanni, Angela Santoni
Chemokines are small chemotactic molecules that play key roles in physiological and pathological conditions. Upon signaling via their specific receptors, chemokines regulate tissue mobilization and trafficking of a wide array of immune cells, including natural killer (NK) cells. Current research is focused on analyzing changes in chemokine/chemokine receptor expression during various diseases to interfere with pathological trafficking of cells or to recruit selected cell types to specific tissues. NK cells are a heterogeneous lymphocyte population comprising several subsets endowed with distinct functional properties and mainly representing distinct stages of a linear development process...
2016: Frontiers in Immunology
Racquel Domingo-Gonzalez, Oliver Prince, Andrea Cooper, Shabaana A Khader
Chemokines and cytokines are critical for initiating and coordinating the organized and sequential recruitment and activation of cells into Mycobacterium tuberculosis-infected lungs. Correct mononuclear cellular recruitment and localization are essential to ensure control of bacterial growth without the development of diffuse and damaging granulocytic inflammation. An important block to our understanding of TB pathogenesis lies in dissecting the critical aspects of the cytokine/chemokine interplay in light of the conditional role these molecules play throughout infection and disease development...
October 2016: Microbiology Spectrum
Undraga Schagdarsurengin, Lisa M Teuchert, Christina Hagenkötter, Nils Nesheim, Temuujin Dansranjavin, Hans-Christian Schuppe, Sabrina Gies, Adrian Pilatz, Wolfgang Weidner, Florian M E Wagenlehner
: Background/Aims/Objectives: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) has detrimental effects on the quality of life including the aspect of sexual dysfunction. The aim of the study was to identify if there was an adverse effect on the male genital compartment and if there are systemic or compartment-specific local signals for epigenetic dysregulation of inflammatory factors in CP/CPPS patients. METHODS: One hundred five NIH IIIb CP/CPPS patients and 41 healthy men were recruited and underwent investigations of urines, semen and blood...
October 20, 2016: Urologia Internationalis
Xiao-Qian Li, Zai-Li Zhang, Wen-Fei Tan, Xi-Jia Sun, Hong Ma
Toll-like receptor 4 (TLR4) is important for the pathogenesis of inflammatory reactions and the promotion of pain processing after ischemia/reperfusion (IR) in spinal cord. Recently, C-X-C chemokine ligand 12 (CXCL12) and its receptor, C-X-C chemokine receptor 4 (CXCR4), were demonstrated to be simultaneously critical for inflammatory reactions, thereby facilitating glial activation. However, whether CXCL12/CXCR4 expression can contribute to IR-induced inflammatory pain via spinal TLR4 remained unclear. A rat model was established by 8 min of aortic arch occlusion...
2016: PloS One
Gabriela Maria Wiedemann, Max Martin Ludwig Knott, Viola Katharina Vetter, Moritz Rapp, Sascha Haubner, Julia Fesseler, Benjamin Kühnemuth, Patrick Layritz, Raffael Thaler, Stephan Kruger, Steffen Ormanns, Doris Mayr, Stefan Endres, David Anz
In cancer patients, immunosuppression through regulatory T cells (Treg) is a crucial component of tumor immune evasion and contributes to disease progression. Tumor-infiltrating Treg in particular suppress local effector T cell responses and are associated with poor prognosis in tumors such as human pancreatic cancer or hepatocellular carcinoma (HCC). The chemokine CCL22 is known to recruit Treg into the tumor tissue and many types of human tumors are known to express high levels of CCL22. The mechanisms leading to intratumoral secretion of CCL22 are so far unknown...
2016: Oncoimmunology
Damla Tokac, Erdem Tuzun, Huseyin Gulec, Vuslat Yılmaz, Elif Sinem Bireller, Bedia Cakmakoglu, Cem Ismail Kucukali
OBJECTIVE: Bipolar disorder (BD) is a debilitating psychiatric disease with unknown etiology. Recent studies have shown inflammation as a potential contributing factor of BD pathogenesis. However, potential associations between chemokine and chemokine receptor polymorphisms and BD have been fundamentally understudied. To identify participation of chemokines in BD pathogenesis, we examined genetic variants of several chemokine and chemokine receptor genes. METHODS: The study population comprised 200 patients with BD and 195 age- and sex-matched healthy controls...
September 2016: Psychiatry Investigation
Ryoyo Ikebuchi, Shunsuke Teraguchi, Alexis Vandenbon, Tetsuya Honda, Francis H W Shand, Yasutaka Nakanishi, Takeshi Watanabe, Michio Tomura
Foxp3(+) regulatory T cells (Tregs) migrating from the skin to the draining lymph node (dLN) have a strong immunosuppressive effect on the cutaneous immune response. However, the subpopulations responsible for their inhibitory function remain unclear. We investigated single-cell gene expression heterogeneity in Tregs from the dLN of inflamed skin in a contact hypersensitivity model. The immunosuppressive genes Ctla4 and Tgfb1 were expressed in the majority of Tregs. Although Il10-expressing Tregs were rare, unexpectedly, the majority of Il10-expressing Tregs co-expressed Gzmb and displayed Th1-skewing...
October 19, 2016: Scientific Reports
Xiao-Pei Yang, Ji-Yang Fu, Rui-Cheng Yang, Wen-Tong Liu, Tao Zhang, Bo Yang, Ling Miao, Bei-Bei Dou, Chen Tan, Huan-Chun Chen, Xiang-Ru Wang
BACKGROUND: Streptococcus suis serotype 2 (SS2) is an important zoonotic bacterial pathogen in both humans and animals, which can cause high morbidity and mortality. Meningitis is one of the major clinical manifestations of SS2 infection. However, the specific process of SS2 meningitis and its molecular mechanisms remain unclear. Epidermal growth factor receptor (EGFR) has been reported to initiate transduction of intracellular signals and regulate host inflammatory responses. Whether and how EGFR contributes to the development of S...
October 19, 2016: Journal of Neuroinflammation
Jie Qin, Yusuke Arakawa, Miwa Morita, John J Fung, Shiguang Qian, Lina Lu
BACKGROUND: Islet transplantation is a promising therapeutic approach for restore the physical response to blood glucose in type 1 diabetes. Current chronic use of immunosuppressive reagents for preventing islet allograft rejection is associated with severe complications. In addition, many of the immunosuppressive drugs are diabetogenic. The induction of transplant tolerance to eliminate the dependency on immunosuppression is ideal, but remains challenging. METHODS: Addition of hepatic stellate cells allowed generation of myeloid-derived suppressor cells (MDSC) from precursors in mouse bone marrow...
October 17, 2016: Transplantation
Lingran Kong, Chengchao Ruan, Pingjin Gao
OBJECTIVE: Inflammatory processes plays a pivotal role in pathogenesis of hypertension. Previous study have indicated that A2A receptor is closely related with immunogenic anti-inflammation process. The present study aimed to elucidate whether the activation of A2A receptor is involved in the regulation of hypertension-induced cardiovascular consequence via regulating immunoresponse. DESIGN AND METHOD: Deoxycorticosterone acetat (DOCA)-salt hypertensive mice were injected intraperitoneally with specific A2A receptor agonist (CGS21680) or antagonist (istradefylline) or PBS respectively...
September 2016: Journal of Hypertension
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