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Kristi J Warren, Xi Fang, Nagaraj M Gowda, Joshua J Thompson, Nicola M Heller
Lung M2 macrophages are regulators of airway inflammation, associated with poor lung function in allergic asthma. Previously, we demonstrated that IL-4-induced M2 gene expression correlated with tyrosine phosphorylation of the insulin receptor substrate (IRS)-2 in macrophages. We hypothesized that negative regulation of IRS-2 activity following IL-4 stimulation is dependent upon serine phosphorylation of IRS-2. Herein, we describe an inverse relationship between tyrosine phosphorylation (pY) and serine phosphorylation (pS) of IRS-2 following IL-4 stimulation...
October 14, 2016: Journal of Biological Chemistry
Megan S Inkeles, Rosane M B Teles, Delila Pouldar, Priscila R Andrade, Cressida A Madigan, David Lopez, Mike Ambrose, Mahdad Noursadeghi, Euzenir N Sarno, Thomas H Rea, Maria T Ochoa, M Luisa Iruela-Arispe, William R Swindell, Tom H M Ottenhoff, Annemieke Geluk, Barry R Bloom, Matteo Pellegrini, Robert L Modlin
Transcriptome profiles derived from the site of human disease have led to the identification of genes that contribute to pathogenesis, yet the complex mixture of cell types in these lesions has been an obstacle for defining specific mechanisms. Leprosy provides an outstanding model to study host defense and pathogenesis in a human infectious disease, given its clinical spectrum, which interrelates with the host immunologic and pathologic responses. Here, we investigated gene expression profiles derived from skin lesions for each clinical subtype of leprosy, analyzing gene coexpression modules by cell-type deconvolution...
September 22, 2016: JCI Insight
Arjun Saha, Susan Buntz, Paula Scotland, Li Xu, Pamela Noeldner, Sachit Patel, Amy Wollish, Aruni Gunaratne, Tracy Gentry, Jesse Troy, Glenn K Matsushima, Joanne Kurtzberg, Andrew E Balber
Microglia and monocytes play important roles in regulating brain remyelination. We developed DUOC-01, a cell therapy product intended for treatment of demyelinating diseases, from banked human umbilical cord blood (CB) mononuclear cells. Immunodepletion and selection studies demonstrated that DUOC-01 cells are derived from CB CD14(+) monocytes. We compared the ability of freshly isolated CB CD14(+) monocytes and DUOC-01 cells to accelerate remyelination of the brains of NOD/SCID/IL2Rγ(null) mice following cuprizone feeding-mediated demyelination...
August 18, 2016: JCI Insight
Jianting Xu, Changyong E, Yongfang Yao, Shuangchun Ren, Guoqing Wang, Haofan Jin
Gastric cancer (GC) is one of the most common types of cancer of the digestive tract. Invasion of tumor cells into surrounding tissue and metastasis are among the most significant checkpoints in tumor progression. It is known that matrix metalloproteinases (MMPs) are involved in these processes; however, knowledge of their molecular interaction networks is still limited. Investigation of these networks could provide a more comprehensive picture of the function of MMPs in tumorigenesis. Furthermore, it could be used to develop new approaches to targeted anticancer therapy...
October 2016: Oncology Letters
Yetrib Hathout, Laurie S Conklin, Haeri Seol, Heather Gordish-Dressman, Kristy J Brown, Lauren P Morgenroth, Kanneboyina Nagaraju, Christopher R Heier, Jesse M Damsker, John N van den Anker, Erik Henricson, Paula R Clemens, Jean K Mah, Craig McDonald, Eric P Hoffman
Corticosteroids are extensively used in pediatrics, yet the burden of side effects is significant. Availability of a simple, fast, and reliable biochemical read out of steroidal drug pharmacodynamics could enable a rapid and objective assessment of safety and efficacy of corticosteroids and aid development of corticosteroid replacement drugs. To identify potential corticosteroid responsive biomarkers we performed proteome profiling of serum samples from DMD and IBD patients with and without corticosteroid treatment using SOMAscan aptamer panel testing 1,129 proteins in <0...
2016: Scientific Reports
Taku Fujimura, Aya Kakizaki, Sadanori Furudate, Setsuya Aiba
Pemphigus vulgaris (PV) and bullous pemphigoid (BP) are autoimmune blistering diseases, and substantial numbers of CD163(+) tissue-associated macrophages (TAMs) are detected in both diseases. PV and BP possess different subsets of helper T cells, suggesting that the cytokine profiles of PV and BP might be different. The purpose of the present study is to investigate the microenvironment of lesional skin and serum of PV and BP patients, focusing on the immunomodulatory factors related to TAMs, such as periostin (POSTN), chemokines, cytokines and matrix metalloproteinases...
August 8, 2016: Experimental Dermatology
Norzana Abd Ghafar, Choy Ker-Woon, Chua Kien Hui, Yasmin Anum Mohd Yusof, Wan Zurinah Wan Ngah
BACKGROUND: The study aimed to evaluate the effects of Acacia honey (AH) on the migration, differentiation and healing properties of the cultured rabbit corneal fibroblasts. METHODS: Stromal derived corneal fibroblasts from New Zealand White rabbit (n = 6) were isolated and cultured until passage 1. In vitro corneal ulcer was created using a 4 mm corneal trephine onto confluent cultures and treated with basal medium (FD), medium containing serum (FDS), with and without 0...
2016: BMC Complementary and Alternative Medicine
Claudius J Wagner, Carsten Schultz, Marcus A Mall
Chronic lung disease remains the major cause of morbidity and mortality in patients with cystic fibrosis (CF). Recent studies in young children with CF diagnosed by newborn screening identified neutrophil elastase (NE), a major product released from neutrophils in inflamed airways, as a key risk factor for the onset and early progression of CF lung disease. However, the understanding of how NE and potentially other proteases contribute to the complex in vivo pathogenesis of CF lung disease remains limited. In this review, we summarize recent progress in this area based on studies in βENaC-overexpressing (βENaC-Tg) mice featuring CF-like lung disease and novel protease-specific Förster resonance energy transfer (FRET) sensors for localization and quantification of protease activity in the lung...
December 2016: Molecular and Cellular Pediatrics
Jie Jia, Thomas M Conlon, Carolina Ballester Lopez, Michael Seimetz, Mariola Bednorz, Zhe Zhou-Suckow, Norbert Weissmann, Oliver Eickelberg, Marcus A Mall, Ali Önder Yildirim
Epidemiological evidence demonstrates a strong link between postnatal cigarette smoke (CS) exposure and increased respiratory morbidity in young children. However, how CS induces early onset airway disease in young children, and how it interacts with endogenous risk factors, remains poorly understood. We, therefore, exposed 10-day-old neonatal wild-type and β-epithelial sodium ion channel (β-ENaC)-transgenic mice with cystic fibrosis-like lung disease to CS for 4 days. Neonatal wild-type mice exposed to CS demonstrated increased numbers of macrophages and neutrophils in the bronchoalveolar lavage fluid (BALF), which was accompanied by increased levels of Mmp12 and Cxcl1 BALF from β-ENaC-transgenic mice contained greater numbers of macrophages, which did not increase following acute CS exposure; however, there was significant increase in airway neutrophilia compared with filtered air transgenic and CS-exposed wild-type controls...
September 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Fee Klupp, Lena Neumann, Christoph Kahlert, Johannes Diers, Niels Halama, Clemens Franz, Thomas Schmidt, Moritz Koch, Juergen Weitz, Martin Schneider, Alexis Ulrich
BACKGROUND: Matrixmetalloproteinases (MMPs) comprise a family of zinc-dependent endopeptidases which are involved in angiogenesis, tumor invasion and metastatic formation. Up to date, the prognostic relevance of MMPs in serum of patients with colon cancer remains unknown. Thus, we wanted to assess an expression pattern of MMPs in a homogenous cohort of colon cancer patients to assess their potential as prognostic biomarkers. METHODS: Differences in the expression pattern of MMP7, MMP10 and MMP12 in 78 serum specimens of patients with an adenocarcinoma of the colon and serum specimens of a healthy control group were assessed using Luminex-100 technologies...
2016: BMC Cancer
Suhee Kim, Sun Hee Ahn, Jin-Sil Lee, Ji-Eun Song, Sung-Hyun Cho, Seunggon Jung, Seon-Kyu Kim, Seok-Ho Kim, Kwang-Pyo Lee, Ki-Sun Kwon, Tae-Hoon Lee
The periodontium undergoes age-related cellular and clinical changes, but the involved genes are not yet known. Here, we investigated age-related genetic changes in gingiva at the transcriptomic level. Genes that were differentially expressed between young and old human gingiva were identified by RNA sequencing and verified by real-time PCR. A total of 1939 mRNA transcripts showed significantly differential expression between young and old gingival tissues. Matrix metalloprotease (MMP) regulation was the top pathway involved in gingival aging...
2016: PloS One
Melina Amor, Veronica Moreno-Viedma, Alisina Sarabi, Nicole G Grün, Bianca Itariu, Lukas Leitner, Irene Steiner, Martin Bilban, Keiichi Kodama, Atul J Butte, Guenther Staffler, Maximilian Zeyda, Thomas M Stulnig
Obesity is strongly associated with metabolic syndrome, a combination of risk factors that predispose to the development of the cardiometabolic diseases: atherosclerotic cardiovascular disease and type 2 diabetes mellitus. Prevention of metabolic syndrome requires novel interventions to address this health challenge. The objective of this study was the identification of candidate molecules for the prevention and treatment of insulin resistance and atherosclerosis, conditions that underlie type 2 diabetes mellitus and cardiovascular disease, respectively...
June 30, 2016: Molecular Medicine
P F Yu, Y Huang, Y Y Han, L Y Lin, W H Sun, A B Rabson, Y Wang, Y F Shi
Mesenchymal stromal cells (MSCs) tend to infiltrate into tumors and form a major component of the tumor microenvironment. Our previous work demonstrated that tumor necrosis factor α (TNFα)-activated MSCs significantly promoted tumor growth. However, the role of TNFα-treated MSCs in tumor metastasis remains elusive. Employing a lung metastasis model of murine breast cancer, we found that TNFα-activated MSCs strikingly enhanced tumor metastasis compared with normal MSCs. We analyzed the chemokine profiles and found that the expression of CCL5, CCR2 and CXCR2 ligands were enhanced in TNFα-activated MSCs...
July 4, 2016: Oncogene
Feifei Ma, Susana Rodriguez, Xavi Buxo, Anna Morancho, Iolanda Riba-Llena, Ana Carrera, Alejandro Bustamante, Dolors Giralt, Joan Montaner, Carmen Martinez, Immaculada Bori, Anna Rosell
OBJECTIVE: To study plasma levels of matrix metalloproteinases (MMPs) as potential markers of recovery during intensive rehabilitation therapy (IRT) after stroke. DESIGN: Prospective and descriptive 3-months follow-up study. SETTING: Rehabilitation unit and research center. PARTICIPANTS: Patients with first-ever ischemic strokes (n=15) enrolled to IRT (≥3 hours per day/5 days per week) and healthy volunteers serving as non-ischemic controls (n=15)...
June 30, 2016: Archives of Physical Medicine and Rehabilitation
Pedro Serralheiro, Elisa Cairrão, Cláudio J Maia, Marina João, Carlos M Costa Almeida, Ignacio Verde
OBJECTIVES: Transforming growth factor-beta1 (TGF-β1) may participate in local chronic inflammatory processes in varicose veins and in venous wall structure modifications through regulation of matrix metalloproteinases (MMP) and their inhibitors (tissue inhibitor of metalloproteinase (TIMP)). The aim of this study was to analyze the effect of TGF-β1 in the vein wall, namely on the gene expression of selected MMP, TIMP and TGF-β1 receptors. METHODS: Healthy vein samples were harvested from eight subjects who underwent coronary bypass graft surgery with great saphenous vein...
June 20, 2016: Phlebology
Saakshi Khattri, Patrick M Brunner, Sandra Garcet, Robert Finney, Steven R Cohen, Margeaux Oliva, Riana Dutt, Judilyn Fuentes-Duculan, Xiuzhong Zheng, Xuan Li, Kathleen M Bonifacio, Norma Kunjravia, Israel Coats, Inna Cueto, Patricia Gilleaudeau, Mary Sullivan-Whalen, Mayte Suárez-Fariñas, James G Krueger, Emma Guttman-Yassky
BACKGROUND: Atopic dermatitis (AD) is the most common inflammatory skin disease, but treatment options for moderate-to-severe disease are limited. Ustekinumab is an IL-12/IL-23p40 antagonist that suppresses Th1, Th17 and Th22 activation, commonly used for psoriasis patients. OBJECTIVE: We sought to assess efficacy and safety of ustekinumab in moderate-to-severe AD patients. METHODS: In this phase II, double-blind, placebo-controlled study, 33 patients with moderate-to-severe AD were randomly assigned to either ustekinumab (n=16) or placebo (n=17), with subsequent crossover at 16wks, and last dose at 32wks...
June 15, 2016: Experimental Dermatology
Katia Jedeon, Sophia Houari, Sophia Loiodice, Thuy Tran Thu, Manon Le Normand, Ariane Berdal, Sylvie Babajko
Enamel defects resulting from environmental conditions and the way of life are public health concerns because of their high prevalence. As their etiology is unclear, the aim of this study was to analyze the various forms of enamel hypomineralization, and to characterize the genes involved in this process to determine the mechanisms involved in disruptions of amelogenesis. We used bisphenol A (BPA) and fluoride as models, both of which are commonly encountered in human populations and used in dentistry. Wistar rats were chronically exposed to 5 µg/kg/day BPA from day 1 of gestation to day 65 after birth (P65) and 5 mM fluoride from P21 to P65...
June 3, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Jimmy Z Shen, James Morgan, Greg H Tesch, Amanda J Rickard, Sophocles Chrissobolis, Grant R Drummond, Peter J Fuller, Morag J Young
Macrophage mineralocorticoid receptor (MR) signaling is an important mediator of cardiac tissue inflammation and fibrosis. The goal of the present study was to determine the cellular mechanisms of MR signaling in macrophages that promote cardiac tissue injury and remodeling. We sought to identify specific markers of MR signaling in isolated tissue macrophages (cardiac, aortic) vs splenic mononuclear cells from wild-type and myeloid MR-null mice given vehicle/salt or deoxycorticosterone (DOC)/salt for 8 weeks...
August 2016: Endocrinology
Tina Tu-Thu Ngoc Nguyen, Oksana Shynlova, Stephen J Lye
Pregnancy, spontaneous term labor (TL), and postpartum (PP) involution are associated with changes in the cellular and extracellular matrix composition of the uterus. Both the uterine smooth muscle (myometrium) and the infiltrating peripheral blood leukocytes involved in the activation of labor secrete extracellular matrix-degrading enzymes (matrix metalloproteinases, MMPs) that can modulate cellular behavior and barrier function. MMP expression is induced by mechanical stretch in several tissues. We hypothesized that the expression and activity of myometrial MMPs and their tissue inhibitors (TIMPs) are modulated in preparation for TL and PP involution and are regulated by mechanical stretch of uterine walls imposed by the growing fetus...
July 2016: Biology of Reproduction
F-J Lv, Y Peng, F L Lim, Y Sun, M Lv, L Zhou, H Wang, Z Zheng, K M C Cheung, V Y L Leung
OBJECTIVE: Recent evidence suggests a role of fibrogenesis in intervertebral disc (IVD) degeneration. We aim to explore if fibrotic genes may serve as IVD degeneration indicators, and if their expression is associated with myofibroblast activity. DESIGN: Transcriptional expression of fibrosis markers (COL1A1, COL3A1, FN1, HSP47, MMP12, RASAL1) were analyzed in degenerated (D) and non-degenerated (ND) human nucleus pulposus (NP) and annulus fibrosus (AF) cells, along with traditional (SOX9, ACAN) and newly established degeneration markers (CDH2, KRT19, KRT18, FBLN1, MGP, and COMP)...
October 2016: Osteoarthritis and Cartilage
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