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Cytokine signaling

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https://www.readbyqxmd.com/read/28641100/bruton-s-tyrosine-kinase-btk-as-a-promising-target-in-solid-tumors
#1
REVIEW
J Molina-Cerrillo, T Alonso-Gordoa, P Gajate, E Grande
Bruton's tyrosine kinase (BTK) is a non-receptor intracellular kinase that belongs to the TEC-family tyrosine kinases together with bone marrow-expressed kinase (BMX), redundant-resting lymphocyte kinase (RLK), and IL-2 inducible T-Cell kinase (ITK). All these proteins play a key role in the intracellular signaling of both B and T lymphocytes. Recently, some preclinical data have demonstrated that BTK is present in certain tumor subtypes and in other relevant cells that are contributing to the tumor microenvironment such as dendritic cells, macrophages, myeloid derived suppressor cells and endothelial cells...
June 9, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28637016/socs1-gene-promoter-methylation-status-is-associated-with-in-stent-restenosis-after-percutaneous-coronary-intervention
#2
Liang Zhou, Ningfu Wang, Hong Li, Guoxin Tong, Jianmin Yang, Lei Lai, Hao Pan, Xianhua Ye, Jinyu Huang
BACKGROUND: Inflammation is involved in the development of In-stent restenosis (ISR) after percutaneous coronary intervention. We aimed to investigate the association between of suppressor of cytokine signaling-1 (SOCS1), a major negative regulator for inflammation, and the occurrence of ISR in Chinese patients. METHODS: We enrolled patients with coronary artery disease who underwent PCI with stenting. PCI procedures were performed successfully and a follow-up angiography was repeated 1 year later to determine ISR presence...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636874/next-generation-matrix-metalloproteinase-inhibitors-novel-strategies-bring-new-prospects
#3
REVIEW
Maxim Levin, Yael Udi, Inna Solomonov, Irit Sagi
Enzymatic proteolysis of cell surface proteins and extracellular matrix (ECM) is critical for tissue homeostasis and cell signaling. These proteolytic activities are mediated predominantly by a family of proteases termed matrix metalloproteinases (MMPs). The growing evidence in recent years that ECM and non-ECM bioactive molecules (e.g., growth factors, cytokines, chemokines, on top of matrikines and matricryptins) have versatile functions redefines our view on the roles matrix remodeling enzymes play in many physiological and pathological processes, and underscores the notion that ECM proteolytic reaction mechanisms represent master switches in the regulation of critical biological processes and govern cell behavior...
June 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28635957/itk-signalling-via-the-ras-irf4-pathway-regulates-the-development-and-function-of-tr1-cells
#4
Weishan Huang, Sabrina Solouki, Nicholas Koylass, Song-Guo Zheng, Avery August
Type 1 regulatory T (Tr1) cells differentiate in response to signals engaging the T cell receptor (TCR), express high levels of the immunosuppressive cytokine IL-10, but not Foxp3, and can suppress inflammation and promote immune tolerance. Here we show that ITK, an important modulator of TCR signalling, is required for the TCR-induced development of Tr1 cells in various organs, and in the mucosal system during parasitic and viral infections. ITK kinase activity is required for mouse and human Tr1 cell differentiation...
June 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28635661/hypoxic-preconditioning-promotes-the-bioactivities-of-mesenchymal-stem-cells-via-the-hif-1%C3%AE-grp78-akt-axis
#5
Jun Hee Lee, Yeo Min Yoon, Sang Hun Lee
Mesenchymal stem cells (MSC) are ideal materials for stem cell-based therapy. As MSCs reside in hypoxic microenvironments (low oxygen tension of 1% to 7%), several studies have focused on the beneficial effects of hypoxic preconditioning on MSC survival; however, the mechanisms underlying such effects remain unclear. This study aimed to uncover the potential mechanism involving 78-kDa glucose-regulated protein (GRP78) to explain the enhanced MSC bioactivity and survival in hindlimb ischemia. Under hypoxia (2% O₂), the expression of GRP78 was significantly increased via hypoxia-inducible factor (HIF)-1α...
June 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28635548/th-17-regulatory-cytokines-il-21-il-23-and-il-6-enhance-neutrophil-production-of-il-17-cytokines-during-asthma
#6
Rabih Halwani, Asma Sultana, Alejandro Vazquez-Tello, Amer Jamhawi, Abeer A Al-Masri, Saleh Al-Muhsen
BACKGROUND: In a subset of severe asthma patients, chronic airway inflammation is associated with infiltration of neutrophils, Th-17 cells and elevated expression of Th-17-derived cytokines (e.g., interleukin [IL]-17, IL-21, IL-22). Peripheral neutrophils from allergic asthmatics are known to express higher IL-17 cytokine levels than those from healthy subjects, but the regulatory mechanisms involved are not well understood. We hypothesize that Th-17 regulatory cytokines could modulate IL-17 expression in neutrophils...
March 2, 2017: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/28635072/plgf-enhances-tlr-dependent-inflammatory-responses-in-human-mononuclear-phagocytes
#7
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/28634844/thrombospondin-1-production-regulates-the-inflammatory-cytokine-secretion-in-thp-1-cells-through-nf-%C3%AE%C2%BAb-signaling-pathway
#8
Tian Xing, Yao Wang, Wen-Jie Ding, Yuan-Ling Li, Xiao-Dong Hu, Cong Wang, Ao Ding, Ji-Long Shen
Thrombospondin-1 (TSP-1) is upregulated in several inflammatory diseases. Recent data have shown that macrophages from TSP-1-deficient mice have a reduced inflammatory phenotype, suggesting that TSP-1 plays a part in macrophage activation. DNA microarray approach revealed that Porphyromonas gingivalis lipopolysaccharide (P. gingivalis LPS) may induce the enhanced TSP-1 expression in human monocytes, suggesting a role of TSP-1-mediated pathogenesis in periodontitis. Until recently, the function of TSP-1 has been a matter of debate...
June 20, 2017: Inflammation
https://www.readbyqxmd.com/read/28634361/uridine-ameliorates-dextran-sulfate-sodium-dss-induced-colitis-in-mice
#9
Manish Kumar Jeengar, Dinesh Thummuri, Mattias Magnusson, V G M Naidu, Srinivas Uppugunduri
Uridine, one of the four components that comprise RNA, has attracted attention as a novel therapeutic modulator of inflammation. However, very little is known about its effect on intestinal inflammation. The aim of the present study was to investigate the potential protective effect of intracolonic administered uridine against DSS induced colitis in male C57BL/6 mice. Intracolonic instillation of 3 doses of uridine 1 mg/Kg (lower dose), 5 mg/Kg (medium dose), and 10 mg/Kg (higher dose) in saline was performed daily...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634110/pharmacological-rescue-of-ductal-cftr-rescue-pancreatic-and-salivary-glands-acinar-cells-and-tissue-function-in-mouse-models-of-autoimmune-diseases
#10
Mei Zeng, Mitchell Szymczak, Malini Ahuja, Changyu Zheng, Hongen Yin, William Swaim, John A Chiorini, Robert J Bridges, Shmuel Muallem
BACKGROUND & AIMS: Sjögren's syndrome and autoimmune pancreatitis (AIP) are disorders with decreased function of salivary, lacrimal glands, and the exocrine pancreas. NOD/ShiLTJ mice and mice transduced with the cytokine BMP6 develop Sjögren's syndrome and chronic pancreatitis and MRL/Mp mice are models of AIP. CFTR is a ductal Cl(-) channel essential for ductal fluid and HCO3(-) secretion. We used these models to ask: is CFTR expression altered in these diseases, does correction of CFTR correct gland function, and most notably, does correcting ductal function correct acinar function...
June 17, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28634033/nickel-sulfate-promotes-il-17a-producing-cd4-t-cells-by-an-il-23-dependent-mechanism-regulated-by-tlr4-and-jak-stat-pathways
#11
Rami Bechara, Diane Antonios, Hayat Azouri, Marc Pallardy
Allergic contact dermatitis, caused by nickel, is a delayed-type hypersensitivity reaction and 14.5% of the general population may be affected in Europe. Among a wide range of cytokines, the IL-12 family has unique structural and immunological characteristics. While IL-12p70 promotes T helper (Th) 1 cells polarization, IL-23 promotes Th17 cells development and both have been isolated from nickel-allergic patients. In this work, we were interested in understanding the mechanism behind nickel-induced Th17 cells development...
June 17, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28632778/over-expressing-the-soluble-gp130-fc-does-not-ameliorate-methionine-and-choline-deficient-diet-induced-non-alcoholic-steatohepatitis-in-mice
#12
Helene L Kammoun, Tamara Louise Allen, Darren Colin Henstridge, Michael James Kraakman, Lone Peijs, Stefan Rose-John, Mark Anthony Febbraio
Non-alcoholic steatohepatitis (NASH) is a liver disease with the potential to lead to cirrhosis and hepatocellular carcinoma. Interleukin-6 (IL-6) has been implicated in the pathogenesis of NASH, with the so-called IL-6 'trans-signaling' cascade being responsible for the pro-inflammatory actions of this cytokine. We aimed to block IL-6 'trans-signaling', using a transgenic mouse that overexpresses human soluble glycoprotein130 (sgp130Fc Tg mice) fed a commonly used dietary model of inducing NASH (methionine and choline deficient-diet; MCD diet) and hypothesized that markers of NASH would be ameliorated in such mice...
2017: PloS One
https://www.readbyqxmd.com/read/28632753/mait-cells-launch-a-rapid-robust-and-distinct-hyperinflammatory-response-to-bacterial-superantigens-and-quickly-acquire-an-anergic-phenotype-that-impedes-their-cognate-antimicrobial-function-defining-a-novel-mechanism-of-superantigen-induced-immunopathology
#13
Christopher R Shaler, Joshua Choi, Patrick T Rudak, Arash Memarnejadian, Peter A Szabo, Mauro E Tun-Abraham, Jamie Rossjohn, Alexandra J Corbett, James McCluskey, John K McCormick, Olivier Lantz, Roberto Hernandez-Alejandro, S M Mansour Haeryfar
Superantigens (SAgs) are potent exotoxins secreted by Staphylococcus aureus and Streptococcus pyogenes. They target a large fraction of T cell pools to set in motion a "cytokine storm" with severe and sometimes life-threatening consequences typically encountered in toxic shock syndrome (TSS). Given the rapidity with which TSS develops, designing timely and truly targeted therapies for this syndrome requires identification of key mediators of the cytokine storm's initial wave. Equally important, early host responses to SAgs can be accompanied or followed by a state of immunosuppression, which in turn jeopardizes the host's ability to combat and clear infections...
June 2017: PLoS Biology
https://www.readbyqxmd.com/read/28631997/expression-and-purification-of-a-functional-porcine-soluble-triggering-receptor-expressed-on-myeloid-cells-1
#14
Hui Li, Shuangshuang Guo, Leyan Yan, Chunhua Meng, Yiyi Hu, Kongwang He, Zhendan Shi
Triggering receptor expressed on myeloid cells 1 (TREM-1) plays a vital role in the pathogen-triggered amplification loop required for proinflammatory responses. Blockade of TREM-1 signaling may inhibit expansion of sepsis and prolong survival of animals. In the present study, the gene of porcine soluble TREM-1 was cloned and expressed in E. coli. After purification, the bioactivity of recombinant porcine soluble TREM-1 was tested in vitro on porcine alveolar macrophages. The results showed that supplementation with the recombinant porcine sTREM-1 protein rapidly and dose-dependently attenuated the upregulation of cytokines (IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12, IL-16, IL-18, and TNF-α) caused by LPS stimulation in the cultured porcine alveolar macrophages...
February 10, 2017: Animal Biotechnology
https://www.readbyqxmd.com/read/28631356/immune-tolerance-effect-in-mesenteric-lymph-node-lymphocytes-of-geniposide-on-adjuvant-arthritis-rats
#15
Zheng-Rong Zhang, Hong Wu, Rong Wang, Shu-Ping Li, Li Dai, Wen-Yu Wang
Rheumatoid arthritis (RA) is a systemic, Th1 cytokine-predominant autoimmune disease result in a chronic and inflammatory disorder. Geniposide (GE), an iridoid glycoside compound that is purified from Gardenia jasminoides Ellis, has antiinflammatory and other immunoregulatory effects, but its exact mechanism of actions on RA is unknown. The aim of this study was to elucidate antiinflammation effects of GE on adjuvant arthritis (AA) rats and its possible immune tolerance mechanisms. Male Sprague-Dawley rats were administered with GE (30, 60, and 120 mg/kg) orally from day 17 to 24 after immunization...
June 19, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28631311/the-il-10-stat3-axis-contributions-to-immune-tolerance-by-thymus-and-peripherally-derived-regulatory-t-cells
#16
REVIEW
Klaus G Schmetterer, Winfried F Pickl
The signal transducer and activator of transcription (STAT) proteins are important mediators for the integration of extrinsic signals provided by cytokines and hormones and thereby adapt cellular processes to their surroundings. In the past decade, the involvement of STAT3 in the regulation of T-cell responses has become a topic of increasing interest. STAT3 is activated in response to multiple cytokines, many of which have been shown to influence T-cell responses. Interestingly, many of these factors have been described with apparent opposing roles, such as the highly pro-inflammatory potency of IL-6 and the anti-inflammatory properties of IL-10, thus raising the possibility that STAT3 signaling may fulfill diverse roles in CD4(+) T-cells...
June 20, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28631090/subclinical-cutaneous-inflammation-remained-after-permeability-barrier-disruption-enhances-uv-sensitivity-by-altering-er-stress-responses-and-topical-pseudoceramide-prevents-them
#17
Sang Eun Lee, Yutaka Takagi, Takahiro Nishizaka, Ji Hwoon Baek, Han Jo Kim, Seung Hun Lee
Stratum corneum forms the UV barrier. The effect of ultraviolet B (UVB) on normal skin was extensively studied; however, its effect on barrier perturbed skin remains undefined. Both barrier perturbation and UVB irradiation induce endoplasmic reticulum (ER) stress and unfolded protein response (UPR) in keratinocytes. Mild ER stress activates homeostatic UPR, while severe ER stress leads to abnormal UPR, promoting apoptosis and inflammation. Here, we investigated UV sensitivity and UVB-induced UPR in barrier-disrupted human skin and the effects of pseudoceramide-dominant emollient on UVB-induced skin responses...
June 19, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28630633/djc-suppresses-advanced-glycation-end-products-induced-jak-stat-signaling-and-ros-in-mesangial-cells
#18
Min Sun, Yan Li, Wenjie Bu, Jindong Zhao, Jianliang Zhu, Lingling Gu, Pingping Zhang, Zhaohui Fang
The antidiabetic properties and anti-inflammatory effects of Danzhi Jiangtang Capsules (DJC) have been demonstrated in clinical and laboratory experiments. In this study, we explored whether DJC can ameliorate advanced glycation end products- (AGEs-) mediated cell injury and the precise mechanisms of DJC in treating diabetic nephropathy (DN). Western blot analysis was employed to assess the expressions of iNOS, COX2, and SOCS and the phosphorylation of JAK2, STAT1, and STAT3 in glomerular mesangial cells (GMCs) after treatment with DJC...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28630460/oxidative-and-endoplasmic-reticulum-stress-is-impaired-in-leukocytes-from-metabolically-unhealthy-vs-healthy-obese-individuals
#19
C Bañuls, S Rovira-Llopis, S Lopez-Domenech, N Diaz-Morales, A Blas-Garcia, S Veses, C Morillas, V M Victor, M Rocha, A Hernandez-Mijares
BACKGROUND: Oxidative stress and inflammation are related to obesity, but the influence of metabolic disturbances on these parameters and their relationship with endoplasmic reticulum (ER) stress is unknown. Therefore, this study was performed to evaluate whether metabolic profile influences ER and oxidative stress in an obese population with/without comorbidities. SUBJECTS AND METHODS: A total of 113 obese patients were enrolled in the study; 29 were metabolically healthy (MHO), 53 were metabolically abnormal (MAO), and 31 had type 2 diabetes (MADO)...
June 20, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28630448/progesterone-prevents-epithelial-mesenchymal-transition-of-ovine-amniotic-epithelial-cells-and-enhances-their-immunomodulatory-properties
#20
Angelo Canciello, Valentina Russo, Paolo Berardinelli, Nicola Bernabò, Aurelio Muttini, Mauro Mattioli, Barbara Barboni
The in vitro expansion is detrimental to therapeutic applications of amniotic epithelial cells (AEC), an emerging source of fetal stem cells. This study provides molecular evidences of progesterone (P4) role in preventing epithelial-mesenchymal transition (EMT) in ovine AEC (oAEC). oAEC amplified under standard conditions spontaneously acquired mesenchymal properties through the up-regulation of EMT-transcription factors. P4 supplementation prevented phenotype shift by inhibiting the EMT-inducing mechanism such as the autocrine production of TGF-β and the activation of intracellular-related signaling...
June 19, 2017: Scientific Reports
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