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IFN-γ signaling

Yuqin Zhang, Guohong Yan, Chengtao Sun, Lihong Nan, Xiaoying Wang, Wei Xu, Kedan Chu
Compound 3R-(4'-hydroxyl-3'-O-β-D-glucopyranosyl phenyl)-dihydro isocoumarin (GDC) is a natural isocoumarin, recently isolated from the stems of H. paniculiflorum. However, we know little about the effects of GDC on rheumatoid arthritis (RA). This study aims to investigate the protective effects and potential mechanisms of GDC against LPS-induced inflammation in vitro. Fibroblast-like synoviocytes (FLSs) obtained from synovial tissue of rats were induced by lipopolysaccharide (LPS) and treated with GDC. Cell viability was determined by mitochondrial-respiration-dependent3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay...
October 17, 2018: Inflammation
Bernice Y Yan, Sandra Garcet, Nicholas Gulati, Felix Kiecker, Judilyn Fuentes-Duculan, Patricia Gilleaudeau, Mary Sullivan-Whalen, Avner Shemer, Hiroshi Mitsui, James G Krueger
Dysplastic nevi (DN) are benign lesions with atypical features intermediate between that of common melanocytic nevi (CMN) and malignant melanoma (MM). Debate remains over whether DN represent progressive lesions from CMN. Through gene expression profiling and analysis of molecular gene signatures, our study revealed progressive increases in immune activation and regulation, along with pathways implicated in melanomagenesis, from CMN to DN to MM. Using criteria of 1.5 fold change and false discovery rate ≤ 0...
October 16, 2018: Experimental Dermatology
Satyavani Kaliamurthi, Gurudeeban Selvaraj, Aman Chandra Kaushik, Ke-Ren Gu, Dong-Qing Wei
Background and aim: Human papillomavirus (HPV) is an oncogenic agent that causes over 90% of cases of cervical cancer in the world. Currently available prophylactic vaccines are type specific and have less therapeutic efficiency. Therefore, we aimed to predict the potential species-specific and therapeutic epitopes from the protein sequences of HPV45 by using different immunoinformatics tools. Methods: Initially, we determined the antigenic potential of late (L1 and L2) and early (E1, E2, E4, E5, E6, and E7) proteins...
2018: Biologics: Targets & Therapy
Xiaoqing Xu, Jia Xu, Jiacheng Wu, Ye Hu, Yanmei Han, Yan Gu, Kai Zhao, Qian Zhang, Xingguang Liu, Juan Liu, Bing Liu, Xuetao Cao
As a critical step during innate response, the cytoplasmic β subunit (IFN-γR2) of interferon-γ receptor (IFN-γR) is induced and translocates to plasma membrane to join α subunit to form functional IFN-γR to mediate IFN-γ signaling. However, the mechanism driving membrane translocation and its significance remain largely unknown. We found, unexpectedly, that mice deficient in E-selectin, an endothelial cell-specific adhesion molecule, displayed impaired innate activation of macrophages upon Listeria monocytogenes infection yet had increased circulating IFN-γ...
September 27, 2018: Cell
Ning Ding, Yuxing Wang, Ce Dou, Feila Liu, Ge Guan, Keyu Wei, Jingyuan Yang, Mingcan Yang, Ju Tan, Wen Zeng, Chuhong Zhu
The in vitro and in vivo effects of physalin D on macrophage M1/M2 polarization were investigated. In silico analysis was first performed for biological function prediction of different physalins. The results suggest physalins have similar predicted biological functions due to their similarities in chemical structures. The cytotoxicity of physalins was then analyzed based on cell apoptosis rate and cell viability evaluation. Physalin D was chosen for further study due to its minimal cytotoxicity. Bone marrow macrophages were isolated and induced with lipopolysaccharide/interferon (IFN)-γ for M1 polarization and interleukin (IL)-4/IL-13 for M2 polarization...
October 14, 2018: Journal of Cellular Physiology
Zhijie Wu, Valentina Giudice, Jichun Chen, Wanling Sun, Zenghua Lin, Keyvan Keyvanfar, Nidhi Talasani, Sachiko Kajigaya, Xingmin Feng, Neal S Young
Interleukin (IL)-18, also known as interferon-gamma (INF-γ)-inducing factor, is involved in Th1 responses and regulation of immunity. Accumulating evidence implicates IL-18 in autoimmune diseases, but little is known of its role in acquired aplastic anemia (AA), immune-mediated destruction of bone marrow (BM) hematopoietic stem and progenitor cells (HSPCs). IL-18 protein levels were significantly elevated in sera of severe AA patients, including both responders and non-responders assayed before treatment, and decreased after treatment...
October 11, 2018: Experimental Hematology
Kaveh Abdi, Karen Laky, Kartika Padhan, Constantinos Petrovas, Jeff Skinner, Juraj Kabat, David W Dorward, Joseph Brzostowski, Eric O Long, Giorgio Trinchieri, Rajat Varma
Early secretion of IL-12 by mouse dendritic cells (DCs) instructs T cells to make IFN-γ. However, only activated, but not naive T cells are able to license DCs for IL-12 production. We hypothesized that it might be due to different levels of CD40L expression on the surface of these cells, as CD40 signals are required for IL-12 production. Using quantitative cell-free systems incorporating CD40L in lipid bilayers combined with total internal reflection fluorescence microscopy and flow cytometry, we show that as low as ∼200 CD40L molecules/μm2 in combination with IL-4 is sufficient to induce IL-12 production by DCs...
October 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Yao Xiao, Guodong Liu, Liansheng Gong
We performed an updated meta-analysis and systematic review to explore the associations between polymorphisms in genes of IL-12 signaling pathway and hepatocellular carcinoma (HCC) risk. Diverse databases were retrieved to identify entire available studies, and odds ratios (ORs) correspondence with 95% confidence intervals (CIs) were performed to assess their associations. Finally, 6 polymorphisms in five genes of the IL-12 signaling pathway were extracted from 39 case-control studies, 26 publications. We identified that STAT4 -rs7574865 polymorphism was significantly associated with an increased risk of HCC in allelic contrast, dominant, homozygote and recessive models...
2018: Journal of Cancer
John Robert Klune, Christian Bartels, Jing Luo, Shin Yokota, Qiang Du, David A Geller
Interleukin-23 (IL-23) is a pro-inflammatory cytokine initially studied in autoimmune disease which has been more recently linked to innate immunity. We observed that the expression of IL-23 is upregulated during hypoxia in hepatocyte and non-parenchymal cell (NPC) co-culture system, as well as during ischemia-reperfusion (I/R) injury in the liver. Interferon regulatory factor-1 (IRF-1) is a transcription factor that induces expression of multiple inflammatory cytokines and has been shown to play a critical role in liver I/R injury...
October 11, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Eduardo Pinheiro Amaral, Érika Machado de Salles, Caio Cesar Barbosa Bomfim, Rafael Moysés Salgado, Fabrício M Almeida, Paula Carolina de Souza, José Maria Alvarez, Mario H Hirata, Elena B Lasunskaia, Maria Regina D'Império-Lima
Background: Tuberculous pneumonia, necrotic granulomatous lesions, and bacterial dissemination characterize severe forms of mycobacterial infection. Methods: To evaluate the pulmonary CD4+ T-cell response during severe tuberculosis, C57BL/6 mice were infected with approximately 100 bacilli of 3 hypervirulent mycobacterial isolates (Mycobacterium tuberculosis strain Beijing 1471 and Mycobacterium bovis strains B2 and MP287/03) or the H37Rv M tuberculosis strain as reference for mycobacterial virulence...
October 11, 2018: Journal of Infectious Diseases
Chrissy M Leopold Wager, Camaron R Hole, Althea Campuzano, Natalia Castro-Lopez, Hong Cai, Marley C Caballero Van Dyke, Karen L Wozniak, Yufeng Wang, Floyd L Wormley
Development of vaccines against opportunistic infections is difficult as patients most at risk of developing disease are deficient in aspects of the adaptive immune system. Here, we utilized an experimental immunization strategy to induce innate memory in macrophages in vivo. Unlike current trained immunity models, we present an innate memory-like phenotype in macrophages that is maintained for at least 70 days post-immunization and results in complete protection against secondary challenge in the absence of adaptive immune cells...
October 10, 2018: PLoS Pathogens
Kandukuri Sowmya, Dev Mala, Mohd Iqbal Bhat, Naveen Kumar, Rajesh Kumar Bajaj, Suman Kapila, Rajeev Kapila
Inflammation and oxidative stress are closely linked patho-physiological processes which occur concurrently in many diseased conditions. Recently, interdependence between these two processes explains the antioxidant paradox associated with failure to select appropriate agents required for prevention of diseases known to be induced by oxidative stress. Present study established the overlapping anti-inflammatory and anti-oxidative potential along with bio-accessibility of milk casein derived tripeptide (LLY)...
September 13, 2018: Journal of Nutritional Biochemistry
Ludovica F Buttó, Li-Guo Jia, Kristen O Arseneau, Hiroshi Tamagawa, Alex Rodriguez-Palacios, Zhaodong Li, Carlo De Salvo, Theresa T Pizarro, Giorgos Bamias, Fabio Cominelli
Background: TNF-like cytokine 1A (TL1A) and its functional receptor, death-domain-receptor-3 (DR3), are multifunctional mediators of effector and regulatory immunity. We aimed to evaluate the functional role and therapeutic potential of TL1A/DR3 signaling in Crohn's disease-like ileitis. Methods: Ileitis-prone SAMP1/YitFc (SAMP) and TNFΔARE/+ mice were rendered deficient for DR3 or TL1A by microsatellite marker-assisted backcrossing. Pathological and immunological characteristics were compared between control and knockout mice, and mucosal immunophenotype was analyzed by Nanostring microarray assay...
October 5, 2018: Inflammatory Bowel Diseases
Lisette Krabbendam, Suzanne M Bal, Hergen Spits, Korneliusz Golebski
Group 2 innate lymphoid cells (ILC2s) are the most well defined group of ILCs. ILC2 development is controlled by the GATA-3 transcription factor and these cells produce archetypal type 2 cytokines, such as IL-5 and IL-13. These cytokines mediate parasite expulsion and tissue repair, but also contribute to type 2 inflammatory diseases, including allergy, asthma and chronic rhinosinusitis with nasal polyps. In response to tightly regulated local environmental cues ILCs can generate characteristics of other subtypes, a process known as plasticity...
November 2018: Immunological Reviews
Hiroki Kabata, Kazuyo Moro, Shigeo Koyasu
Group 2 innate lymphoid cells (ILC2s) play critical roles in the induction of type 2 inflammation, response to parasite infection, metabolic homeostasis, and tissue repair. These multifunctional roles of ILC2s are tightly controlled by complex regulatory systems in the local microenvironment, the disruption of which may cause various health problems. This review summarizes up-to-date knowledge regarding positive and negative regulators for ILC2s based on their function and signaling pathways, including activating cytokines (IL-33, IL-25; MAPK, NF-κB pathways), co-stimulatory cytokines (IL-2, IL-7, IL-9, TSLP; STAT5, IL-4; STAT6, TNF superfamily; MAPK, NF-κB pathways), suppressive cytokines (type1 IFNs, IFN-γ, IL-27; STAT1, IL-10, TGF-β), transdifferentiation cytokines (IL-12; STAT4, IL-1β, IL-18), lipid mediators (LTC4, LTD4, LTE4, PGD2; Ca2+ -NFAT pathways, PGE2, PGI2; AC/cAMP/PKA pathways, LXA4, LTB4), neuropeptides (NMU; Ca2+ -NFAT, MAPK pathways, VIP, CGRP, catecholamine, acetylcholine), sex hormones (androgen, estrogen), nutrients (butyrate; HDAC inhibitors, vitamins), and cell-to-cell interactions (ICOSL-ICOS; STAT5, B7-H6-NKp30, E-cadherin-KLRG1)...
November 2018: Immunological Reviews
Arun Chauhan, Yuyang Sun, Pramod Sukumaran, Fredice O Quenum Zangbede, Christopher N Jondle, Atul Sharma, Dustin L Evans, Pooja Chauhan, Randolph E Szlabick, Mary O Aaland, Lutz Birnbaumer, Jyotika Sharma, Brij B Singh, Bibhuti B Mishra
Macrophage plasticity is essential for innate immunity, but in-depth signaling mechanism(s) regulating their functional phenotypes are ill-defined. Here we report that interferon (IFN) γ priming of naive macrophages induces store-mediated Ca2+ entry and inhibition of Ca2+ entry impairs polarization to M1 inflammatory phenotype. In vitro and in vivo functional analyses revealed ORAI1 to be a primary contributor to basal Ca2+ influx in macrophages, whereas IFNγ-induced Ca2+ influx was mediated by TRPC1. Deficiency of TRPC1 displayed abrogated IFNγ-induced M1 inflammatory mediators in macrophages...
September 20, 2018: iScience
Daniel Kerage, Megan S F Soon, Brianna L Doff, Takumi Kobayashi, Michael D Nissen, Pui Yeng Lam, Graham R Leggatt, Stephen R Mattarollo
Immunomodulatory therapies can effectively control haematological malignancies. Previously we reported the effectiveness of combination immunotherapies that centre on 4-1BB-targeted co-stimulation of CD8 + T cells, particularly when simultaneously harnessing the immune adjuvant properties of Natural Killer T (NKT) cells. The objective of this study was to assess the effectiveness of agonistic anti-4-1BB antibody-based combination therapy against two aggressive forms of acute myeloid leukemia (AML). Anti-4-1BB treatment alone resulted in transient suppression of established AML-ETO9a tumor growth in 50% of mice, however the majority of these mice subsequently succumbed to disease...
2018: Oncoimmunology
Junjun Shen, Tao Yang, Youzhi Xu, Yi Luo, Xinyue Zhong, Limin Shi, Tao Hu, Tianyi Guo, Ying Nie, Feijun Luo, Qinlu Lin
δ-Tocotrienol, an important component of vitamin E, has been reported to possess some physiological functions, such as anticancer and anti-inflammation, however their molecular mechanisms are not clear. In this study, δ-tocotrienol was isolated and purified from rice bran. The anti-inflammatory effect and mechanism of δ-tocotrienol against lipopolysaccharides (LPS) activated pro-inflammatory mediator expressions in RAW264.7 cells were investigated. Results showed that δ-tocotrienol significantly inhibited LPS-stimulated nitric oxide (NO) and proinflammatory cytokine (TNF-α, IFN-γ, IL-1β and IL-6) production and blocked the phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular regulated protein kinases 1/2 (ERK1/2)...
October 4, 2018: International Journal of Molecular Sciences
Xiao-Di Tang, Duo-Duo Zhang, Linpei Jia, Wei Ji, Yu-Shuang Zhao
BACKGROUND/AIMS: Accumulating evidence has highlighted the importance of long non-coding RNAs (lncRNAs) as competing endogenous RNAs (ceRNAs) in tumor biology. Among others, actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) has been associated with non-small cell lung cancer (NSCLC). However, it remains unclear how AFAP1-AS1 participates in the development and progression of NSCLC. METHODS: The peripheral blood samples were collected from patients with NSCLC...
October 2, 2018: Cellular Physiology and Biochemistry
Hui Xuan Lim, Hak-Jun Jung, Arim Lee, Si Hoon Park, Byung Woo Han, Daeho Cho, Tae Sung Kim
In addition to essential roles in protein synthesis, lysyl-tRNA synthetase (KRS) is secreted to trigger a proinflammatory function that induces macrophage activation and TNF-α secretion. KRS has been associated with autoimmune diseases such as polymyositis and dermatomyositis. In this study, we investigated the immunomodulatory effects of KRS on bone marrow-derived dendritic cells (DCs) of C57BL/6 mice and subsequent polarization of Th cells and analyzed the underlying mechanisms. KRS-treated DCs increased the expression of cell surface molecules and proinflammatory cytokines associated with DC maturation and activation...
October 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
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