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Miao Qiu, Keqing Huang, Yanzhuo Liu, Yuqing Yang, Honglin Tang, Xiaoxiao Liu, Chenlong Wang, Honglei Chen, Yu Xiong, Jing Zhang, Jing Yang
High-fat diet (HFD) promotes lung pre-metastatic niche formation and metastasis. Thus, there is an urgent need to identify the underlying mechanisms and develop strategies to overcome them. Here we demonstrate that glycyrrhizic acid (GA) prevents HFD-enhanced pre-metastatic niche formation and metastasis through gut microbiota. GA reduced HFD-enhanced myeloid-derived suppressor cell recruitment, pro-metastatic protein S100A8/A9 expression and metastasis burden of 4T1 breast cancer and B16F10 melanoma, accompanied by gut microbiota alteration and colonic macrophage polarization far away the M1-like phenotype...
February 12, 2019: Mucosal Immunology
I Wayan Sumardika, Youyi Chen, Nahoko Tomonobu, Rie Kinoshita, I Made Winarsa Ruma, Hiroki Sato, Eisaku Kondo, Yusuke Inoue, Akira Yamauchi, Hitoshi Murata, Ken-Ichi Yamamoto, Shuta Tomida, Kazuhiko Shien, Hiromasa Yamamoto, Junichi Soh, Junichiro Futami, Endy Widya Putranto, Toshihiko Hibino, Masahiro Nishibori, Shinichi Toyooka, Masakiyo Sakaguchi
Compiling evidence indicates an unusual role of extracellular S100A8/A9 in cancer metastasis. S100A8/A9 secreted from either cancer cells or normal cells including epithelial and inflammatory cells stimulates cancer cells through S100A8/A9 sensor receptors in an autocrine or paracrine manner, leading to cancer cell metastatic progression. We previously reported a novel S100A8/A9 receptor, neuroplastin-β (NPTNβ), which plays a critical role in atopic dermatitis when it is highly activated in keratinocytes by an excess amount of extracellular S100A8/A9 in the inflammatory skin lesion...
February 5, 2019: Molecular Carcinogenesis
Gopalkrishna Sreejit, Sunil Kiran Nooti, Baskaran Athmanathan, Prabhakara Reddy Nagareddy
S100A8/A9 represents a novel biomarker and therapeutic target in sterile inflammatory diseases. Among the various S100 proteins, S100A8 and S100A9 have been shown to be the most important of all the damage-associated molecular pattern (DAMP) proteins in sterile inflammatory conditions such as diabetes, cardiovascular disease, autoimmune disorders, etc. We present here methods to quantify S100A8/A9 expression in various tissues in mouse models of myocardial infarction (MI) using flow cytometry (FC), immunofluorescence, quantitative real-time polymerase chain reaction (q-RT-PCR), and enzyme-linked immunosorbent assays (ELISA)...
2019: Methods in Molecular Biology
Elizabeth Elder, Benjamin Krishna, James Williamson, Yusuf Aslam, Neda Farahi, Alexander Wood, Veronika Romashova, Kate Roche, Eain Murphy, Edwin Chilvers, Paul J Lehner, John Sinclair, Emma Poole
One site of latency of human cytomegalovirus (HCMV) in vivo is in undifferentiated cells of the myeloid lineage. Although latently infected cells are known to evade host T cell responses by suppression of T cell effector functions, it is not known if they must also evade surveillance by other host immune cells. Here we show that cells latently infected with HCMV can, indeed, be killed by host neutrophils but only in a serum-dependent manner. Specifically, antibodies to the viral latency-associated US28 protein mediate neutrophil killing of latently infected cells...
January 8, 2019: iScience
Mingqun Qin, Yantao Zou, Kanghua Zhong, Yong Guo, Xianqiong Zou
Calprotectin in mucosal epidermal keratinocytes has an important role in fighting microbial infections. S100A8 belongs to the S100 protein family and is a subunit of calprotectin (heterodimer complex of S100A8/A9). Interleukin‑1α (IL‑1α) is one of the cytokines produced by oral keratinocytes. The primary aims of the present study were to investigate the effect of IL‑1α on the expression of S100A8 and its underlying molecular mechanism in oral epithelial cells. Determining the molecular mechanism of the induced expression of S100A8 by IL‑1α aims to improve current understanding of the roles of calprotectin during the infection of mucosal epithelial cells...
January 15, 2019: Molecular Medicine Reports
Chloe J Taub, Marc E Lippman, Barry I Hudson, Bonnie B Blomberg, Alain Diaz, Hannah M Fisher, Erica R Nahin, Suzanne C Lechner, Taekyoung Kwak, Gyong Ha Hwang, Michael H Antoni
BACKGROUND: Women with breast cancer (BCa) experience heightened distress, which is related to greater inflammation and poorer outcomes. The s100 protein family facilitates the inflammatory response by regulating myeloid cell function through the binding of Toll-like receptor 4 and the receptor for advanced glycation end products (RAGE). The heterodimer s100A8/A9 RAGE ligand is associated with hastened tumor development and metastasis. Previously, a 10-week stress-management intervention using cognitive behavioral therapy (CBT) and relaxation training (RT) was associated with less leukocyte inflammatory gene expression in patients with BCa; however, its impact on s100A8/A9 was not examined...
January 11, 2019: Cancer
Xiangbin Zheng, Xia Huo, Yu Zhang, Qihua Wang, Yuling Zhang, Xijin Xu
Lead (Pb) and polycyclic aromatic hydrocarbon (PAH) exposure is positively associated with cardiovascular disease (CVD), and the possible potential mechanism may be caused by damage to the endothelium by modulation of inflammatory processes. No comprehensive research shows co-exposure of Pb and PAH on cardiovascular endothelial inflammation in electronic waste (e-waste) exposed populations. Given this, the aim of this study is to provide evidence for a relationship between Pb and PAH co-exposure and cardiovascular endothelial inflammation, in an e-waste-exposed population, to delineate the link between a potential mechanism for CVD and environmental exposure...
December 19, 2018: Environmental Pollution
Kabeerdoss Jayakanthan, Thomas Meera, Goel Ruchika, Mohan Hindumathi, Danda Sumita, L Jeyaseelan, Danda Debashish
BACKGROUND: Toll-like receptors (TLR) 1 to 4 are highly expressed in aorta. Activation of TLR4 causes transmural arteritis in Human temporal artery-SCID chimera model. Neither TLR-4 nor its ligands have been studied in TA patients as yet. Aim of this study was to examine the expression of TLR4 and its endogenous ligands in peripheral blood mononuclear cells (PBMCs) of patients with Takayasu arteritis (TA). METHODS: mRNA expression of TLR4, RAGE and various endogenous TLR4 ligands were quantified in PBMCs of 24 TA patients and 19 sex and age matched healthy controls by real time PCR using specific primers and SYBR Green qPCR master mix...
December 26, 2018: Cytokine
Sandeep Karna, Yoo Jin Shin, Sungtae Kim, Hyun-Duck Kim
AIM: This study aims to evaluate the association of salivary S100A8 and A9 proteins with periodontitis and its screening ability for periodontitis cross-sectionally. MATERIAL AND METHODS: We selected 326 participants from the Yanypyeong Cohort: 218 participants with periodontitis and 108 participants without periodontitis. Stage II-IV periodontitis according to the modification of new international classification of periodontitis was considered as periodontitis...
December 27, 2018: Journal of Clinical Periodontology
Yiyi Ye, Lixia Pei, Jing Ding, Chunyu Wu, Chenping Sun, Sheng Liu
Activation of the inflammatory signaling pathway is the most vital part of the pre-metastatic events of breast cancer. Platycodin D (PlaD) shows favorable pharmacological activities in anti-inflammatory and anti-tumor effect. The main purpose of this study was to survey the effects of PlaD on S100A8/A9-induced inflammation in mouse mammary carcinoma 4T1 cells. S100A8/A9 immunolocalization and expression in pre-metastatic lung tissue were assessed by immunofluorescence staining and ELISA. 4T1 cells were treated with 2...
December 15, 2018: International Immunopharmacology
Taoufik Nedjadi, Anthony Evans, Adnan Sheikh, Lawrence Barerra, Suliman Al-Ghamdi, Lucy Oldfield, W Greenhalf, John P Neoptolemos, Eithne Costello
BACKGROUND: The secretion of soluble factors enables communication between tumour cells and the surrounding microenvironment and plays an important role in oncogenesis. Pancreatic ductal adenocarcinoma (PDAC) is characterised by a highly reactive microenvironment, harbouring a variety of cell types, including S100A8/S100A9-expressing monocytes. S100A8/S100A9 proteins regulate the behaviour of cancer cells by inducing pre-metastatic cascades associated with cancer spread. The aim of this study was to examine how S100A8/A9 proteins mediate tumour-stroma crosstalk in PDAC...
December 17, 2018: BMC Cancer
Ji Won Kim, JaeSang Ko, JinJoo Kim, Jin Sook Yoon
PURPOSE: Early detection and control of inflammation are important to manage Graves' orbitopathy (GO). We investigated the effects of calprotectin (S100A8/A9) on orbital fibroblast inflammation and GO pathogenesis. METHODS: We measured serum calprotectin, S100A8 and S100A9 mRNA expression in orbital fat/connective tissue from GO patients and healthy controls, and proinflammatory cytokines in primary cultured orbital fibroblasts. RESULTS: The serum levels of S100A8/A9 and the expression of S100A8/A9 mRNA in orbital tissue were higher in the GO patients than in the healthy controls...
November 19, 2018: Ocular Immunology and Inflammation
Xiaonan Chen, Ting Tao, Hongyan Wang, Hongyu Zhao, Lin Lu, Fang Wu
BACKGROUND The aim of this study was to determine the involvement of S100A8/A9 in the development of arterial thrombosis. MATERIAL AND METHODS A total of 303 patients were enrolled in this study, with 110 having acute coronary syndrome (ACS) and 110 having coronary heart disease (CHD), and 83 subjects served as healthy blood donors. The concentrations of Toll-like receptor 4 (TLR-4), cyclooxygenase-2 (COX-2), and S100A8/A9 protein were determined in the sera of the participants and in peripheral blood mononuclear cells (PBMCs) derived from a rat carotid artery thrombosis model and in human aortic endothelial cells (HAECs)...
October 27, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Rie Kinoshita, Hiroki Sato, Akira Yamauchi, Yuta Takahashi, Yusuke Inoue, I Wayan Sumardika, Youyi Chen, Nahoko Tomonobu, Kota Araki, Kazuhiko Shien, Shuta Tomida, Hidejiro Torigoe, Kei Namba, Eisuke Kurihara, Yusuke Ogoshi, Hitoshi Murata, Ken-Ichi Yamamoto, Junichiro Futami, Endy Widya Putranto, I Made Winarsa Ruma, Hiromasa Yamamoto, Junichi Soh, Toshihiko Hibino, Masahiro Nishibori, Eisaku Kondo, Shinichi Toyooka, Masakiyo Sakaguchi
Within the "seed and soil" theory of organ tropic cancer metastasis is a growing compilation of evidence that S100A8/A9 functions as a soil signal that attracts cancer cells to certain organs, which prove beneficial to their growth. S100A8/A9-sensing receptors including Toll-like receptor 4 (TLR4), advanced glycation end products (RAGE), and also important receptors we recently succeeded in identifying (EMMPRIN, NPTNβ, ΜCAM, and ALCAM) have the potential to become promising therapeutic targets. In our study, we prepared extracellular regions of these novel molecules and fused them to human IgG2-Fc to extend half-life expectancy, and we evaluated the anti-metastatic effects of the purified decoy proteins on metastatic cancer cells...
October 26, 2018: International Journal of Cancer. Journal International du Cancer
Meili Wu, Lu Xu, Yu Wang, Ning Zhou, Fei Zhen, Ying Zhang, Xuebin Qu, Hongbin Fan, Sihan Liu, Yan Chen, Ruiqin Yao
S100A8/A9, a heterodimer complex composed of calcium-binding proteins S100A8 and S100A9, is significantly increased in the serum of multiple sclerosis (MS) patients. Relevant reports have revealed that MS pathology is commonly associated with the activation of microglial cells and the damage of oligodendrocyte precursor cells (OPCs). Moreover, microglia activation following stimulation increases the expression of pro-inflammatory cytokines, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), which further exacerbate the damage to OPCs...
September 25, 2018: Brain Research Bulletin
Dirk Holzinger, Dirk Foell, Christoph Kessel
S100A8/A9 and S100A12 are released from activated monocytes and granulocytes and act as proinflammatory endogenous toll-like receptor (TLR)4-ligands. S100 serum concentrations correlate with disease activity, both during local and systemic inflammatory processes. In some autoinflammatory diseases such as familial Mediterranean fever (FMF) or systemic juvenile idiopathic arthritis (SJIA), dysregulation of S100 release may be involved in the pathogenesis. Moreover, S100 serum levels are a valuable supportive tool in the diagnosis of SJIA in fever of unknown origin...
September 25, 2018: Molecular and Cellular Pediatrics
Claas H Hinze, Dirk Foell, Anne L Johnson, Steven J Spalding, Beth S Gottlieb, Paula W Morris, Yukiko Kimura, Karen Onel, Suzanne C Li, Alexei A Grom, Janalee Taylor, Hermine I Brunner, Jennifer L Huggins, James J Nocton, Kathleen A Haines, Barbara S Edelheit, Michael Shishov, Lawrence K Jung, Calvin B Williams, Melissa S Tesher, Denise M Costanzo, Lawrence S Zemel, Jason A Dare, Murray H Passo, Kaleo C Ede, Judyann C Olson, Elaine A Cassidy, Thomas A Griffin, Linda Wagner-Weiner, Jennifer E Weiss, Larry B Vogler, Kelly A Rouster-Stevens, Timothy Beukelman, Randy Q Cron, Daniel Kietz, Kenneth Schikler, Jay Mehta, Tracy V Ting, James W Verbsky, Anne B Eberhard, Bin Huang, Edward H Giannini, Daniel J Lovell
OBJECTIVE: To determine the relationship between serum S100A8/A9 and S100A12 and the maintenance of clinical inactive disease (CID) in patients with polyarticular forms of juvenile idiopathic arthritis (PF-JIA) while on anti-tumor necrosis factor therapy (anti-TNF) and disease flare following withdrawal of anti-TNF. METHODS: In this prospective, multicenter study, 137 patients with PF-JIA were enrolled while in CID on anti-TNF. Patients were observed for the initial 6 months...
September 18, 2018: Arthritis & Rheumatology
S C M van Dalen, N N L Kruisbergen, B Walgreen, M M A Helsen, A W Slöetjes, N A J Cremers, M I Koenders, F A J van de Loo, J Roth, T Vogl, A B Blom, P M van der Kraan, P L E M van Lent, M H J van den Bosch
OBJECTIVE: Synovitis in collagenase-induced osteoarthritis (CiOA) is driven by locally released S100A8/A9 proteins and enhances joint destruction. S100A8/A9 can induce reactive oxygen species (ROS) release by phagocytes in OA synovium via neutrophil cytosolic factor-1 (Ncf1)-regulated NOX2 activation. In the present study we investigated whether NOX2-derived ROS affect joint pathology during CiOA. METHODS: CiOA was induced in knee joints of wild type (WT) and Ncf1-deficient (Ncf1**) mice...
September 5, 2018: Osteoarthritis and Cartilage
Ibon Eguíluz-Gracia, Kristiina Malmstrom, Sinan Ahmed Dheyauldeen, Jouko Lohi, Antti Sajantila, Ragnhild Aaløkken, Arvind Y M Sundaram, Gregor D Gilfillan, Mika Makela, Espen S Baekkevold, Frode L Jahnsen
BACKGROUND: Activated T helper type 2 (Th2) cells are believed to play a pivotal role in allergic airway inflammation, but which cells attract and activate Th2 cells locally have not been fully determined. Recently, it was shown in an experimental human model of allergic rhinitis (AR) that activated monocytes rapidly accumulate in the nasal mucosa after local allergen challenge, where they promote recruitment of Th2 cells and eosinophils. OBJECTIVE: To investigate whether monocytes are recruited to the lungs in paediatric asthma...
September 5, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
Kazufumi Nakamura, Masakiyo Sakaguchi, Hiromi Matsubara, Satoshi Akagi, Toshihiro Sarashina, Kentaro Ejiri, Kaoru Akazawa, Megumi Kondo, Koji Nakagawa, Masashi Yoshida, Toru Miyoshi, Takeshi Ogo, Takahiro Oto, Shinichi Toyooka, Yuichiro Higashimoto, Kei Fukami, Hiroshi Ito
BACKGROUND: Pulmonary vascular remodeling of pulmonary arterial hypertension (PAH) is characterized by an inappropriate increase of vascular cells. The receptor for advanced glycation end products (RAGE) is a type I single-pass transmembrane protein belonging to the immunoglobulin superfamily and is involved in a broad range of hyperproliferative diseases. RAGE is also implicated in the etiology of PAH and is overexpressed in pulmonary artery smooth muscle cells (PASMCs) in patients with PAH...
2018: PloS One
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