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Macrophage activation

Rui Yamaguchi, Arisa Sakamoto, Reona Yamaguchi, Misa Haraguchi, Shinji Narahara, Hiroyuki Sugiuchi, Yasuo Yamaguchi
The stimuli inducing expression of single immunoglobulin IL-1-related receptor (SIGIRR) and the relevant regulatory mechanisms are not well defined. Transforming growth factor β1 (TGFβ1) delays internalization of neurokinin-1 receptor (NK1R) and subsequently enhances cellular signaling. This study investigated the effect of TGFβ1 on SIGIRR protein production by human M1 macrophages in response to stimulation with substance P (SP). SP caused upregulation of SIGIRR expression in a concentration-dependent manner, whereas aprepitant (an NK1R inhibitor) blunted this response...
March 17, 2018: Cytokine
Honglin Jin, Chao Wan, Zhenwei Zou, Guifang Zhao, Lingling Zhang, Yuanyuan Geng, Tong Chen, Ai Huang, Fagang Jiang, Jue-Ping Feng, Jonathan F Lovell, Jing Chen, Gang Wu, Kunyu Yang
Immunosuppressive tumor microenvironments (TMEs) create tremendous obstacles for an effective cancer therapy. Herein, we developed a melittin-RADA32 hybrid peptide hydrogel loaded with doxorubicin (DOX) for a potent chemoimmunotherapy against melanoma through the active regulation of TMEs. The formed melittin-RADA32-DOX (MRD) hydrogel has an interweaving nanofiber structure and exhibits excellent biocompatibility, controlled drug release properties both in vitro and in vivo, and an enhanced killing effect to melanoma cells...
March 20, 2018: ACS Nano
Shelly A Cruz, Zhaohong Qin, Alexandre F R Stewart, Hsiao-Huei Chen
Ischemic brain injury triggers neuronal cell death by apoptosis via caspase activation and by necroptosis through activation of the receptor-interacting protein kinases (RIPK) associated with the tumor necrosis factor-alpha (TNF-α)/death receptor. Recent evidence shows RIPK inhibitors are neuroprotective and alleviate ischemic brain injury in a number of animal models, however, most have not yet undergone clinical trials and safety in humans remains in question. Dabrafenib, originally identified as a B-raf inhibitor that is currently used to treat melanoma, was later revealed to be a potent RIPK3 inhibitor at micromolar concentrations...
February 2018: Neural Regeneration Research
Elizabeth Ann Misch, Christopher Saddler, James Muse Davis
PURPOSE OF REVIEW: This review describes recent trends in the epidemiology of nontuberculous mycobacteria (NTM), emerging pathogens, new insights into NTM pathogenesis, and advances in diagnosis and treatment. RECENT FINDINGS: Emerging pathogens include Mycobacterium chimaera and drug-resistant subspecies of Mycobacterium abscessus. Important virulence mechanisms of pathogenic NTM include the ability to alter the macrophage's permissiveness to intracellular bacterial growth...
March 19, 2018: Current Infectious Disease Reports
Lu Gan, Yanan Yang, Qian Li, Yi Feng, Tianshu Liu, Weijian Guo
Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase and a catalytic component of PRC2, catalyzes tri-methylation of histone H3 at Lys 27 (H3K27me3) to regulate gene expression through epigenetic machinery. EZH2 also functions both as a transcriptional suppressor and a transcriptional co-activator, depending on H3K27me3 or not and on the different cellular contexts. Unsurprisingly, numerous studies have highlighted the role of EZH2 in cancer development and progression. Through modulating critical gene expression, EZH2 promotes cell survival, proliferation, epithelial to mesenchymal, invasion, and drug resistance of cancer cells...
2018: Biomarker Research
Ill-Min Chung, Sung-Kyu Park, Mohd Ali, Mayakrishnan Prabakaran, Young-Tek Oh, Seung-Hyun Kim, Nasir Ali Siddiqui, Ateeque Ahmad
Five new flavonoids namely, 5-hydroxy-6-isoprenyl-7,4'-dimethoxyflavonol-3- O - β -d-arabinofuranoside ( 1 ), 5,7-dihydroxy-4'-methoxyflavone-7- O - β -d-arabinopyranosyl-2''- n -decan-1'''-oate ( 2 ), 3-butanoyl-5,6,8-trihydroxy-7,4'-dimethoxyflavonol--5- O - β -d-glucopyranoside ( 3 ), 7, 4'-dimethoxy-5-hydroxyflavone-5- O - α -d-arabinopyranosyl-(2'' → 1''')- O - α -d-arabinopyranoside ( 4 ), and 5,6-dihydroxy-7, 4'-dimethoxyflavone-5- O - α -d-glucopyranoside ( 5 ), together with two known compounds, were isolated from the methanol extract of Oryza sativa leaves and straw...
March 2018: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
María M Banda, Carolina López, Rubiceli Manzo, Gadea Rico-Pérez, Pablo García, Roberto Rosales-Reyes, Miguel A De la Cruz, Fernando C Soncini, Francisco García-Del Portillo, Víctor H Bustamante
When Salmonella is grown in the nutrient-rich lysogeny broth (LB), the AraC-like transcriptional regulator HilD positively controls the expression of genes required for Salmonella invasion of host cells, such as the Salmonella pathogenicity island 1 (SPI-1) genes. However, in minimal media, the two-component system PhoP/Q activates the expression of genes necessary for Salmonella replication inside host cells, such as the SPI-2 genes. Recently, we found that the SL1344_1872 hypothetical gene, located in a S...
March 19, 2018: Scientific Reports
Akihiko Kimura, Yuko Ishida, Machi Furuta, Mizuho Nosaka, Yumi Kuninaka, Akira Taruya, Naofumi Mukaida, Toshikazu Kondo
BACKGROUND: A clear understanding of the molecular mechanisms underlying hemodynamic stress-initiated cardiac hypertrophy is important for preventing heart failure. Interferon-γ (IFN-γ) has been suggested to play crucial roles in various diseases other than immunological disorders by modulating the expression of myriad genes. However, the involvement of IFN-γ in the pathogenesis of cardiac hypertrophy still remains unclear. METHODS AND RESULTS: In order to elucidate the roles of IFN-γ in pressure overload-induced cardiac pathology, we subjected Balb/c wild-type (WT) or IFN-γ-deficient ( Ifng -/- ) mice to transverse aortic constriction (TAC)...
March 19, 2018: Journal of the American Heart Association
Valérie Besnard, Alain Calender, Diane Bouvry, Yves Pacheco, Catherine Chapelon-Abric, Florence Jeny, Hilario Nunes, Carole Planès, Dominique Valeyre
BACKGROUND: Sarcoidosis is a systemic disease characterized by the formation of immune granulomas in various organs, mainly the lungs and the lymphatic system. Exaggerated granulomatous reaction might be triggered in response to unidentified antigens in individuals with genetic susceptibility. The present study aimed to determine the genetic variants implicated in a familial case of sarcoidosis. METHODS: Sarcoidosis presentation and history, NOD2 profile, NF-κB and cytokine production in blood monocytes/macrophages were evaluated in individuals from a family with late appearance of sarcoidosis...
March 20, 2018: Respiratory Research
Ashraf M Abdel-Moneim, Mohamed A Al-Kahtani, Omar M Elmenshawy, Hany Elsawy, Aly M Hafez, Marwa A Genena
In this field study, the levels of heavy metals (Pb, Fe, Co, Cu, and Zn) in water and a suite of biochemical and histological biomarkers in the grouper ( Epinephelus tauvina) were assessed at four sites in the Arabian Gulf. Samples were taken from a relatively non-urban reference site, called Salwa (S1), and three effluent-dominated sites, namely Al-aziziyah in southern Dammam city (S2), the Al-Jubail coast (S3), and Manifa (S4). Toxic metals, namely Pb and Co (at all sites) and Fe (at S3), were elevated in water samples relative to the internationally permissible limits...
January 1, 2018: Toxicology and Industrial Health
Sabrina G Müller, Natália S Jardim, Caroline B Quines, Cristina W Nogueira
Bisphenol A (BPA) is a chemical toxicant that has deleterious effects on human. BPA causes oxidative stress in tissues, including the liver. Diphenyl diselenide (PhSe)2 improves the antioxidant response via activation of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/Kelch-like ECH-associated protein (keap 1) pathway in macrophage cells. In the present study, we investigated whether (PhSe)2 counteracts hepatic oxidative stress induced by BPA in male and female Swiss mice. Three-week-old mice received by the intragastric (i...
March 16, 2018: Environmental Research
Nathalie Fournier, Emilie Jacque, Alexandre Fontayne, Delphine Derache, Gilles Dupont, Lucie Verhaeghe, Linda Baptista, Aurélie Dehenne, Anne-Sophie Dezetter, Aurélie Terrier, Alain Longue, Virginie Pochet-Beghin, Cecile Beghin, Sami Chtourou, Christophe de Romeuf
Plasmacytoid dendritic cells (pDCs) play a central role for both innate and adaptive antiviral responses, as they direct immune responses through their unique ability to produce substantial concentrations of type I interferon (IFNs) upon viral encounter while also activating multiple immune cells, including macrophages, DCs, B, natural killer and T cells. Recent evidence clearly indicates that pDCs also play a crucial role in some cancers and several auto-immune diseases. Although treatments are currently available to patients with such pathologies, many are not fully efficient...
March 19, 2018: MAbs
Michelle E Maxson, Xenia Naj, Teresa R O'Meara, Jonathan D Plumb, Leah E Cowen, Sergio Grinstein
Candida albicans hyphae can reach enormous lengths, precluding their internalization by phagocytes. Nevertheless, macrophages engulf a portion of the hypha, generating incompletely sealed tubular phagosomes. These frustrated phagosomes are stabilized by a thick cuff of F-actin that polymerizes in response to non-canonical activation of integrins by fungal glycan. Despite their continuity, the surface and invaginating phagosomal membranes retain a strikingly distinct lipid composition. PtdIns(4,5)P2 is present at the plasmalemma but is not detectable in the phagosomal membrane, while PtdIns(3)P and PtdIns(3,4,5)P3 co-exist in the phagosomes yet are absent from the surface membrane...
March 19, 2018: ELife
Peter D Koch, Howard R Miller, Gary Yu, John A Tallarico, Peter K Sorger, Yuan Wang, Yan Feng, Jason R Thomas, Nathan T Ross, Timothy Mitchison
We screened a library of bioactive small molecules for activators and inhibitors of innate immune signaling through IRF3 and NFkB pathways with the goals of advancing pathway understanding and discovering probes for immunology research. We used high content screening to measure the translocation from the cytoplasm to nucleus of IRF3 and NFkB in primary human macrophages; these transcription factors play a critical role in the activation of STING and other pro-inflammatory pathways. Our pathway activator screen yielded a diverse set of hits that promoted nuclear translocation of IRF3 and/or NFkB, but the majority of these compounds did not cause activation of downstream pathways...
March 19, 2018: ACS Chemical Biology
Yukio Fujiwara, Yoichi Saito, Takuya Shiota, Pan Cheng, Tsuyoshi Ikeda, Koji Ohnishi, Motohiro Takeya, Yoshihiro Komohara
Recent progress in anti-tumor therapy has revealed the significance of anti-tumor immune responses in tumor progression and clinical course in several kinds of malignant tumors. The draining lymph node is an important immune system component that contains a number of antigen-presenting cells, which induce rapid immune responses to foreign antigens. Current studies have shown that higher expression of CD169 on lymph node sinus macrophages is associated with the induction of anti-tumor immunity. In the present study, we searched for natural compounds that regulate the CD169-positive phenotype in macrophages to identify potential new anti-cancer agents targeting macrophage activation...
2018: Journal of Clinical and Experimental Hematopathology: JCEH
Nikolaos G Frangogiannis
Inflammation plays a crucial role in cardiac repair, but may also extend ischemic injury and contribute to post-infarction remodeling. This review manuscript discusses recent advances in our understanding of the cell biology of the post-infarction inflammatory response. Recently published studies demonstrated that the functional repertoire of inflammatory and reparative cells may extend beyond the roles suggested by traditional teachings. Neutrophils may play an important role in cardiac repair by driving macrophages toward a reparative phenotype...
February 2018: Current Opinion in Physiology
Zhou Zhou, Ming-Jiang Xu, Yan Cai, Wei Wang, Joy X Jiang, Zoltan V Varga, Dechun Feng, Pal Pacher, George Kunos, Natalie J Torok, Bin Gao
Background & Aims: Hepatic infiltration of neutrophils is a hallmark of steatohepatitis; however, the role of neutrophils in the progression of steatohepatitis remains unknown. Methods: A clinically relevant mouse model of steatohepatitis induced by high-fat diet (HFD) plus binge ethanol feeding was used. Liver fibrosis was examined. In vitro cell culture was used to analyze the interaction of hepatic stellate cells (HSCs) and neutrophils. Results: HFD plus one binge ethanol (HFD+1B) feeding induced significant hepatic neutrophil infiltration, liver injury, and fibrosis...
March 2018: Cellular and Molecular Gastroenterology and Hepatology
Franchesca Cruz-Pérez, Salvador Vilá, Grissel Ríos, Luis M Vilá
Macrophage-activating syndrome (MAS) is a rare condition characterized by dysfunctional macrophage activation leading to overproduction of cytokines and phagocytosis of erythrocytes, leukocytes, and platelets. MAS is associated with infectious diseases, malignancies, and autoimmune rheumatic disorders. Herein, we present a 22-year-old Hispanic woman with SLE who was hospitalized because of a three-week history of fever, fatigue, polyarthralgia, nausea, and abdominal pain. Initial laboratories showed severe pancytopenia with marked elevation of liver enzymes and ferritin levels...
2018: Case Reports in Rheumatology
Malgorzata Pieniazek, Rafal Matkowski, Piotr Donizy
Cutaneous melanoma is an aggressive cancer and its onset and growth are associated, through direct and indirect interactions, with the cancer microenvironment. The microenvironment comprises a dynamic complex of numerous types of cells (due to histogenesis) that constantly interact with each other through multiple cytokines and signaling proteins. Macrophages are one of the most thoroughly studied pleiotropic cells of the immune system. One of their major cytophysiological functions is their involvement in phagocytosis...
April 2018: Oncology Letters
Hak-Jae Kim, Chun-Geon Park, Rakesh Varghese, Ji Yeon Lee, YoungOck Kim, Gi-Ho Sung
The leaf of Aurea helianthus ( A. helianthus Jinhuakui) is popularly used in China traditional medicine, however, scientific evidence on its antioxidant properties rarely studied. In this study, biological activities of A. helianthus leave's 80% ethanol extract (AHL) were investigated. The measured total polyphenol and flavonoid content of AHL was 184.24 ± 5.01 mg GAE/g and 102.53 ± 0.98 mg NAR/g. AHL showed the highest α, α -diphenyl- β -picrylhydrazyl (DPPH) and 2,2'-azino-bis-3-ethylbenzo-thiazoline-6-sulfonic acid (ABTS) radical scavenging activities of 98...
December 2017: Saudi Journal of Biological Sciences
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