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Zong-Mei Bian, Matthew G Field, Susan G Elner, Victor M Elner
Human retinal pigment epithelial (hRPE) cells play important immune-regulatory roles in a variety of retinal pathologic processes, including the production of inflammatory cytokines that are essential mediators of the innate immune response within the ocular microenvironment. The pro-inflammatory "alarmin" cytokine IL-1α has been implicated in both infectious and non-infectious retinal diseases, but its regulation in the retina is poorly understood. The purpose of this study was to elucidate the expression and regulation of IL-1α within hRPE cells...
March 15, 2018: Experimental Eye Research
Aigli G Vakrakou, Sorina Boiu, Panayiotis D Ziakas, Evangelia Xingi, Haralabia Boleti, Menelaos N Manoussakis
Sjögren's syndrome (SS) patients manifest high cell-free DNA (cf-DNA) levels in serum, associated with impaired DNaseI activity. Undegraded DNA may accumulate in tissues and act as an inflammasome-activating signal. Herein, we investigated the occurrence of aberrant DNA build-up in various biologic compartments of SS patients and its correlation with the activity of NLRP3 and AIM2 inflammasomes. For this purpose, we evaluated sera, PBMC, circulating monocytes and salivary glands (SG) from different SS patient subgroups and controls...
March 15, 2018: Journal of Autoimmunity
Fayin Tang, Kefeng Fan, Kunli Wang, Chuanzhou Bian
Acute lung injury (ALI) arises from uncontrolled pulmonary inflammation with high mortality rates. Atractylodin (Atr) is a polyethylene alkynes and has been reported to possess anti-inflammation effect. Thus, we aimed to investigate the protective effect of Atr on lipopolysaccharide (LPS)-induced inflammatory responses ALI. The results indicated that Atr treatment not only significantly attenuated LPS-stimulated histopathological changes but also lessened the myeloperoxidase (MPO) activity, the wet-to-dry weight ratio of the lungs, protein leakage and infiltration of inflammatory cells...
February 2, 2018: Journal of Pharmacological Sciences
Hong Jun Park, Jiye Kim, Fatema Tuj Saima, Ki-Jong Rhee, Soonjae Hwang, Moon Young Kim, Soon Koo Baik, Young Woo Eom, Hyun-Soo Kim
Inflammatory bowel disease (IBD) is an idiopathic disease caused by a dysregulated immune response to intestinal microbes in an individual with a genetic predisposition. Therefore, alleviation of inflammation is very important to treat IBD. Mesenchymal stem cells (MSCs) have been highlighted as new candidates for treating autoimmune disease based on their immunomodulatory properties. In this study, we investigated the anti-inflammatory mechanism and therapeutic effects of adipose tissue-derived MSCs (ASCs) using THP-1 macrophages and dextran sodium sulfate (DSS)-induced mice with chronic colitis...
March 15, 2018: Biochemical and Biophysical Research Communications
Haipeng Yin, Qiang Guo, Xin Li, Tiantian Tang, Cuiling Li, Hengxiao Wang, Yuanxin Sun, Qi Feng, Chunhong Ma, Chengjiang Gao, Fan Yi, Jun Peng
Turmeric is traditionally used as a spice and coloring in foods. Curcumin is the primary active ingredient in the turmeric, and compelling evidence has shown that it has the ability to inhibit inflammation. However, the mechanism mediating its anti-inflammatory effects are not fully understood. We report that curcumin inhibited caspase-1 activation and IL-1β secretion through suppressing LPS priming and the inflammasome activation pathway in mouse bone marrow-derived macrophages. The inhibitory effect of curcumin on inflammasome activation was specific to the NLRP3, not to the NLRC4 or the AIM2 inflammasomes...
March 16, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Chun Wang, Susan Hockerman, E Jon Jacobsen, Yael Alippe, Shaun R Selness, Heidi R Hope, Jeffrey L Hirsch, Stephen J Mnich, Matthew J Saabye, William F Hood, Sheri L Bonar, Yousef Abu-Amer, Ariela Haimovich, Hal M Hoffman, Joseph B Monahan, Gabriel Mbalaviele
p38α activation of multiple effectors may underlie the failure of global p38α inhibitors in clinical trials. A unique inhibitor (CDD-450) was developed that selectively blocked p38α activation of the proinflammatory kinase MK2 while sparing p38α activation of PRAK and ATF2. Next, the hypothesis that the p38α-MK2 complex mediates inflammasome priming cues was tested. CDD-450 had no effect on NLRP3 expression, but it decreased IL-1β expression by promoting IL-1β mRNA degradation. Thus, IL-1β is regulated not only transcriptionally by NF-κB and posttranslationally by the inflammasomes but also posttranscriptionally by p38α-MK2...
March 16, 2018: Journal of Experimental Medicine
Gaetan Barbet, Leif E Sander, Matthew Geswell, Irina Leonardi, Andrea Cerutti, Iliyan Iliev, J Magarian Blander
Live vaccines historically afford superior protection, yet the cellular and molecular mechanisms mediating protective immunity remain unclear. Here we found that vaccination of mice with live, but not dead, Gram-negative bacteria heightened follicular T helper cell (Tfh) differentiation, germinal center formation, and protective antibody production through the signaling adaptor TRIF. Complementing the dead vaccine with an innate signature of bacterial viability, bacterial RNA, recapitulated these responses...
March 9, 2018: Immunity
Fawaz Awad, Eman Assrawi, Camille Louvrier, Claire Jumeau, Irina Giurgea, Serge Amselem, Sonia-Athina Karabina
Photoaging and epithelial skin tumorigenesis are complex processes triggered mainly by UV radiation from chronic sun exposure. This leads to DNA damage and reactive oxygen species (ROS) production, which initiate an inflammatory response that alters cell structure and function. Changes in cell homeostasis and ROS production activate intracellular multiprotein platforms called inflammasomes. Inflammasomes nucleate around cytoplasmic receptors mainly of the NLR (nucleotide-binding domain and leucine-rich repeat) family and regulate caspase-1-dependant secretion of pro-inflammatory interleukin (IL)-1β and IL-18 cytokines, and an inflammatory form of death named pyroptosis...
March 12, 2018: Mechanisms of Ageing and Development
Ruiting Li, Jing Wang, Ruifang Li, Fangfang Zhu, Wenjuan Xu, Gan Zha, Guangzhen He, Huan Cao, Yimin Wang, Jiong Yang
The ATP/P2X7 axis of dendritic cells (DCs) mediates the activation of NLRP3 inflammasome and promotes secretion of interleukin (IL)-1β and IL-18 to induce T helper (Th) 2, Th17 differentiation in the pathogenesis of asthma. NLRP3 inflammasome also regulates high mobility protein 1 (HMGB1) release in DCs. Recent studies demonstrated the correlation between HMGB1 expression and airway inflammation and hyper-responsiveness (AHR) in asthma. However, the relationship between the ATP/P2X7-NLRP3 axis and HMGB1 in DCs in asthma is still unclear...
March 12, 2018: Experimental Cell Research
Quan-Bo Zhang, Yu-Feng Qing, Cong-Cong Yin, Li Zhou, Xian-Shuang Liu, Qing-Sheng Mi, Jing-Guo Zhou
BACKGROUND: MicroRNAs (miRNAs) serve as important regulators of inflammatory and immune responses and are implicated in several immune disorders including gouty arthritis. The expression of miR-146a is upregulated in the peripheral blood mononuclear cells of patients with inter-critical gout when compared to normouricemic and hyperuricemic controls and those patients with acute gout flares. However, the role of miR-146a in the development of gout remains unknown. Here, we used miR-146a knockout (KO) mice to test miR-146a function in a monosodium urate (MSU)-induced gouty arthritis model...
March 15, 2018: Arthritis Research & Therapy
Takuya Wakamatsu, Suguru Yamamoto, Toru Ito, Yoko Sato, Koji Matsuo, Yoshimitsu Takahashi, Yoshikatsu Kaneko, Shin Goto, Junichiro James Kazama, Fumitake Gejyo, Ichiei Narita
In chronic kidney disease (CKD) patients, accumulation of uremic toxins is associated with cardiovascular risk and mortality. One of the hallmarks of kidney disease-related cardiovascular disease is intravascular macrophage inflammation, but the mechanism of the reaction with these toxins is not completely understood. Macrophages differentiated from THP-1 cells were exposed to indoxyl sulfate (IS), a representative uremic toxin, and changes in inflammatory cytokine production and intracellular signaling molecules including interleukin (IL)-1, aryl hydrocarbon receptor (AhR), nuclear factor (NF)-κ, and mitogen-activated protein kinase (MAPK) cascades as well as the NLRP3 inflammasome were quantified by real-time PCR, Western blot analysis, and enzyme-linked immunosorbent assay...
March 15, 2018: Toxins
Vahid Mirshafiee, Bingbing Sun, Chong Hyun Chang, Yu-Pei Liao, Wen Jiang, Jinhong Jiang, Xiangsheng Liu, Xiang Wang, Tian Xia, Andre E Nel
The liver and the mononuclear phagocyte system (MPS) is a frequent target for engineered nanomaterials (ENMs), either as a result of particle uptake and spread from primary exposure sites or systemic administration of therapeutic and imaging nanoparticles. In this study, we performed a comparative analysis of the toxicological impact of 29 metal oxide (MOx) nanoparticles (NPs), some commonly used in consumer products, in transformed or primary Kupffer cells (KCs) and hepatocytes. Not only did we observe differences between KC and hepatocytes, but also differences in the toxicological profiles of transition metal oxides (TMOs, e...
March 15, 2018: ACS Nano
Alexia Eyraud, Brigitte Milpied, Denis Thiolat, Anne-Sophie Darrigade, Katia Boniface, Alain Taïeb, Julien Seneschal
Folliculitis decalvans (FD) is a chronic inflammatory disease leading to scarring alopecia with poorly defined pathogenesis. The aim of this study was to investigate the expression of markers associated with the activation of innate immune signals, such as inflammasome (NALP1 and NALP3), interleukin (IL)-1β and IL-8 and type I interferon (MxA). A retrospective monocentric study was conducted and included 17 patients with FD with available biopsies. Disease activity (stable vs. active) was defined clinically and histologically...
March 15, 2018: Acta Dermato-venereologica
John R Apps, Gabriela Carreno, Jose Mario Gonzalez-Meljem, Scott Haston, Romain Guiho, Julie E Cooper, Saba Manshaei, Nital Jani, Annett Hölsken, Benedetta Pettorini, Robert J Beynon, Deborah M Simpson, Helen C Fraser, Ying Hong, Shirleen Hallang, Thomas J Stone, Alex Virasami, Andrew M Donson, David Jones, Kristian Aquilina, Helen Spoudeas, Abhijit R Joshi, Richard Grundy, Lisa C D Storer, Márta Korbonits, David A Hilton, Kyoko Tossell, Selvam Thavaraj, Mark A Ungless, Jesus Gil, Rolf Buslei, Todd Hankinson, Darren Hargrave, Colin Goding, Cynthia L Andoniadou, Paul Brogan, Thomas S Jacques, Hywel J Williams, Juan Pedro Martinez-Barbera
Adamantinomatous craniopharyngiomas (ACPs) are clinically challenging tumours, the majority of which have activating mutations in CTNNB1. They are histologically complex, showing cystic and solid components, the latter comprised of different morphological cell types (e.g. β-catenin-accumulating cluster cells and palisading epithelium), surrounded by a florid glial reaction with immune cells. Here, we have carried out RNA sequencing on 18 ACP samples and integrated these data with an existing ACP transcriptomic dataset...
March 14, 2018: Acta Neuropathologica
Paulino Alvarez, Alexandros Briasoulis
PURPOSE OF REVIEW: Immune system activation plays a central role in heart failure progression. Large-scale immune modulatory clinical trials targeting tumor necrosis factor-α and broad spectrum immune modulation have been negative. The objective of this review is to highlight past, present, and what is in the horizon for the immunomodulation in heart failure with a focus of biologics. RECENT FINDINGS: Strategies targeting interleukin-1 pathway are currently undergoing clinical evaluation and data from pilot studies are promising...
March 15, 2018: Current Treatment Options in Cardiovascular Medicine
Raffaella Mastrocola, Ilario Ferrocino, Erica Liberto, Fausto Chiazza, Alessia Sofia Cento, Debora Collotta, Giulia Querio, Debora Nigro, Valeria Bitonto, Juan Carlos Cutrin, Kalliopi Rantsiou, Mariaconcetta Durante, Emanuela Masini, Manuela Aragno, Chiara Cordero, Luca Cocolin, Massimo Collino
Despite clinical findings suggesting that the form (liquid versus solid) of the sugars may significantly affect the development of metabolic diseases, no experimental data are available on the impact of their formulations on gut microbiota, integrity and hepatic outcomes. In the present sudy, C57Bl/6j mice were fed a standard diet plus water (SD), a standard diet plus 60% fructose syrup (L-Fr) or a 60% fructose solid diet plus water (S-Fr) for 12 weeks. Gut microbiota was characterized through 16S rRNA phylogenetic profiling and shotgun sequencing of microbial genes in ileum content and related volatilome profiling...
February 13, 2018: Journal of Nutritional Biochemistry
Nilubon Singhto, Rattiyaporn Kanlaya, Angkhana Nilnumkhum, Visith Thongboonkerd
In kidney stone disease, macrophages secrete various mediators via classical secretory pathway and cause renal interstitial inflammation. However, whether their extracellular vesicles, particularly exosomes, are involved in kidney stone pathogenesis remained unknown. This study investigated alterations in exosomal proteome of U937-derived macrophages (by phorbol-12-myristate-13-acetate activation) after exposure to calcium oxalate monohydrate (COM) crystals for 16-h using 2-DE-based proteomics approach. Six significantly altered proteins in COM-treated exosomes were successfully identified by nanoscale liquid chromatography-electrospray ionization-electron transfer dissociation tandem mass spectrometry as proteins involved mainly in immune processes, including T-cell activation and homeostasis, Fcγ receptor-mediated phagocytosis, interferon-γ (IFN-γ) regulation, and cell migration/movement...
2018: Frontiers in Immunology
Gregory B Lim
No abstract text is available yet for this article.
March 13, 2018: Nature Reviews. Cardiology
Zlatka Georgieva Dobreva, Boncho Grigorov Grigorov, Spaska Angelova Stanilova
BACKGROUND: Interleukin-18 (IL-18) and Tumor Necrosis Factor-alpha (TNF-α) are proinflammatory cytokines that increased the development of Th1 immune response, but have a different type of regulation of the gene expression. Whereas TNF-α has an inducible expression, IL-18 is translated as an inactive protein and required proteolytic cleavage by Casp-1 in inflammasome complexes. AIM: To investigate the effect of the histone deacetylases inhibitor Suberoylanilide Hydroxamic Acid (SAHA) on the gene expression and secretion of both cytokines, IL-18 and TNF-α, according to their contribution to the cancer development and anticancer immunity...
February 15, 2018: Open Access Macedonian Journal of Medical Sciences
Yi Huang, Hua Jiang, Yun Chen, Xiaqiong Wang, Yanqing Yang, Jinhui Tao, Xianming Deng, Gaolin Liang, Huafeng Zhang, Wei Jiang, Rongbin Zhou
The dysregulation of NLRP3 inflammasome can cause uncontrolled inflammation and drive the development of a wide variety of human diseases, but the medications targeting NLRP3 inflammasome are not available in clinic. Here, we show that tranilast (TR), an old anti-allergic clinical drug, is a direct NLRP3 inhibitor. TR inhibits NLRP3 inflammasome activation in macrophages, but has no effects on AIM2 or NLRC4 inflammasome activation. Mechanismly, TR directly binds to the NACHT domain of NLRP3 and suppresses the assembly of NLRP3 inflammasome by blocking NLRP3 oligomerization...
March 12, 2018: EMBO Molecular Medicine
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