Medicine and Health Sciences Commons^™

Variants In Cxcr4 Associate With Juvenile Idiopathic Arthritis Susceptibility., Terri H. Finkel, Jin Li, Zhi Wei, Wei Wang, Haitao Zhang, Edward M. Behrens, Emma L. Reuschel, Sophie Limou, Carol Wise, Marilynn Punaro, Mara L. Becker, Jane E. Munro, Berit Flatø, Øystein Førre, Susan D. Thompson, Carl D. Langefeld, David N. Glass, Joseph T. Glessner, Cecilia E. Kim, Edward Frackelton, Debra K. Shivers, Kelly A. Thomas, Rosetta M. Chiavacci, Cuiping Hou, Kexiang Xu, James Snyder, Haijun Qiu, Frank Mentch, Kai Wang, Cheryl A. Winkler, Benedicte A. Lie, Justine A. Ellis, Hakon Hakonarson

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease among children, the etiology of which involves a strong genetic component, but much of the underlying genetic determinants still remain unknown. Our aim was to identify novel genetic variants that predispose to JIA.

METHODS: We performed a genome-wide association study (GWAS) and replication in a total of 1166 JIA cases and 9500 unrelated controls of European ancestry. Correlation of SNP genotype and gene expression was investigated. Then we conducted targeted resequencing of a candidate locus, among a subset of 480 cases and 480 controls. SUM test was performed …

Initial Benchmarking Of The Quality Of Medical Care In Childhood-Onset Systemic Lupus Erythematosus., Rina Mina, Julia G. Harris, Marisa S. Klein-Gitelman, Simone Appenzeller, Maraisa Centeville, Diane Eskra, Jennifer L. Huggins, Anne L. Johnson, Raju Khubchandani, Prachi Khandekar, Jiha Lee, Hai Mei Liu, Joshua D. Pendl, Clovis A. Silva, Marco F. Silva, Ahmad I. Zaal, Esi Morgan Dewitt, Stacy P. Ardoin, Hermine I. Brunner

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To assess the quality of medical care in childhood-onset systemic lupus erythematosus (SLE) at tertiary pediatric rheumatology centers as measured by observance of SLE quality indicators (SLE-QIs).

METHODS: International consensus has been achieved for childhood-onset SLE-QIs capturing medical care provision in 9 domains: diagnostic testing, education of cardiovascular (CV) risk and lifestyles, lupus nephritis (LN), medication management, bone health, ophthalmologic surveillance, transition, pregnancy, and vaccination. Using medical record information, the level of performance of these childhood-onset SLE-QIs was assessed in childhood-onset SLE populations treated at 4 tertiary pediatric rheumatology centers in the US, 2 in Brazil, and 1 center …

Stress Granules And Rna Processing Bodies Are Novel Autoantibody Targets In Systemic Sclerosis, Michael E. Johnson, Andrew V. Grassetti, Jaclyn N. Taroni, Shawn M. Lyons, Devin Schweppe, Jessica K. Gordon, Robert F. Speira, Robert Lafyatis, Paul J. Anderson, Scott A. Gerber, Michael L. Whitfield

Dartmouth Scholarship

Autoantibody profiles represent important patient stratification markers in systemic sclerosis (SSc). Here, we performed serum-immunoprecipitations with patient antibodies followed by mass spectrometry (LC-MS/MS) to obtain an unbiased view of all possible autoantibody targets and their associated molecular complexes recognized by SSc.

Endothelial Cells Expressing Endothelial And Mesenchymal Cell Gene Products In Lung Tissue From Patients With Systemic Sclerosis-Associated Interstitial Lung Disease., Fabian A. Mendoza, Sonsoles Piera-Velazquez, John L. Farber, Carol Feghali-Bostwick, Sergio A. Jimenez

Department of Dermatology and Cutaneous Biology Faculty Papers

OBJECTIVE: To examine whether lung endothelial cells (ECs) from patients with systemic sclerosis (SSc)-associated interstitial lung disease (ILD) express mesenchymal cell-specific proteins and gene transcripts, indicative of the occurrence of endothelial-to-mesenchymal phenotypic transition (EndoMT).

METHODS: Lung tissue from 6 patients with SSc-associated pulmonary fibrosis was examined by histopathology and immunohistochemistry. Confocal laser microscopy was utilized to assess the simultaneous expression of EC and myofibroblast molecular markers. CD31+CD102+ ECs were isolated from the lung tissue of 2 patients with SSc-associated ILD and 2 normal control subjects, and the expression of EC and mesenchymal cell markers and other relevant genes was analyzed …

Effect Of Mycophenolate Mofetil On The White Blood Cell Count And The Frequency Of Infection In Systemic Lupus Erythematosus., Ananta Subedi, Laurence S. Magder, Michelle Petri

Department of Medicine Faculty Papers

Leukopenia is a common manifestation of SLE. Addition of immunosuppressive therapy in a SLE patient who is already leukopenic is a clinical concern. It could worsen leukopenia, increase the risk of infection, or both. The aim of this study was to analyze the immediate effect of mycophenolate mofetil on the white blood cell count and the rate of infection in SLE patients. Two hundred and forty-four patients within the Hopkins Lupus Cohort who were newly started on mycophenolate mofetil were included in the study. The white blood cell count and interval infection history on the day mycophenolate mofetil was started …

The Role Played By Cell-Substrate Interactions In The Pathogenesis Of Osteoclast-Mediated Peri-Implant Osteolysis, Zhenxin Shen, Tania N. Crotti, Kevin P. Mchugh, Kenichiro Matsuzaki, Ellen M. Gravallese, Benjamin E. Bierbaum, Steven R. Goldring

Ellen M. Gravallese

Prosthetic wear debris-induced peri-implant osteolysis is a major cause of aseptic loosening after total joint replacement. In this condition, wear particles released from the implant components induce a granulomatous inflammatory reaction at the interface between implant and adjacent bone, leading to progressive bone resorption and loss of fixation. The present study was undertaken to characterize definitively the phenotype of osteoclast-like cells associated with regions of peri-implant focal bone resorption and to compare the phenotypic features of these cells with those of mononucleated and multinucleated cells associated with polyethylene wear particles. Peri-implant tissues were obtained from patients undergoing hip revision surgery …

The Role Of Tnf-Receptor Family Members And Other Traf-Dependent Receptors In Bone Resorption, Ellen M. Gravallese, Deborah L. Galson, Steven R. Goldring, Philip E. Auron

Ellen M. Gravallese

The contribution of osteoclasts to the process of bone loss in inflammatory arthritis has recently been demonstrated. Studies in osteoclast biology have led to the identification of factors responsible for the differentiation and activation of osteoclasts, the most important of which is the receptor activator of NF-kappa B ligand/osteoclast differentiation factor (RANKL/ODF), a tumor necrosis factor (TNF)-like protein. The RANKL/ODF receptor, receptor activator of NF-kappa B (RANK), is a TNF-receptor family member present on both osteoclast precursors and mature osteoclasts. Like other TNF-family receptors and the IL-1 receptor, RANK mediates its signal transduction via TNF receptor-associated factor (TRAF) proteins, suggesting …

Mechanisms Of Bone Loss In Inflammatory Arthritis: Diagnosis And Therapeutic Implications, Steven R. Goldring, Ellen M. Gravallese

Ellen M. Gravallese

Rheumatoid arthritis represents an excellent model in which to gain insights into the local and systemic effects of joint inflammation on skeletal tissues. Three forms of bone disease have been described in rheumatoid arthritis. These include: focal bone loss affecting the immediate subchondral bone and bone at the joint margins; periarticular osteopenia adjacent to inflamed joints; and generalized osteoporosis involving the axial and appendicular skeleton. Although these three forms of bone loss have several features in common, careful histomorphometric and histopathological analysis of bone tissues from different skeletal sites, as well as the use of urinary and serum biochemical markers …

Gene Expression Changes Reflect Clinical Response In A Placebo-Controlled Randomized Trial Of Abatacept In Patients With Diffuse Cutaneous Systemic Sclerosis, Eliza F. Chakravarty, Viktor Martyanov, David Fiorentino, Tammara A. Wood, David J. Haddon, Justin A. Jarrell, Paul Utz, Mark Genovese, Michael Whitfield, Lorinda Chung

Dartmouth Scholarship

Systemic sclerosis is an autoimmune disease characterized by inflammation and fibrosis of the skin and internal organs. We sought to assess the clinical and molecular effects associated with response to intravenous abatacept in patients with diffuse cutaneous systemic.

Role Of Cellular Senescence And Nox4-Mediated Oxidative Stress In Systemic Sclerosis Pathogenesis., Sonsoles Piera-Velazquez, Sergio A. Jimenez

Department of Dermatology and Cutaneous Biology Faculty Papers

Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by progressive fibrosis of skin and numerous internal organs and a severe fibroproliferative vasculopathy resulting frequently in severe disability and high mortality. Although the etiology of SSc is unknown and the detailed mechanisms responsible for the fibrotic process have not been fully elucidated, one important observation from a large US population study was the demonstration of a late onset of SSc with a peak incidence between 45 and 54 years of age in African-American females and between 65 and 74 years of age in white females. Although it is not appropriate …

The Impact Of Waist Circumference On Function And Physical Activity In Older Adults: Longitudinal Observational Data From The Osteoarthritis Initiative, John A. Batsis, Alicia J. Zbehlik, Laura K. Barre, Todd A. Mackenzie, Stephen J. Bartels

Dartmouth Scholarship

Background: We previously demonstrated that BMI is associated with functional decline and reduced quality of life. While BMI in older adults is fraught with challenges, waist circumference (WC) is a marker of visceral adiposity that can also predict mortality. However, its association with function and quality of life in older adults is not well understood and hence we sought to examine the impact of WC on six-year outcomes.

Methods: We identified adults aged ≥60 years from the longitudinal Osteoarthritis Initiative and stratified the cohort into quartiles based on WC. Our primary outcome measures of function at six year follow-up included: …

A Prospective Observational Study Of Mycophenolate Mofetil Treatment In Progressive Diffuse Cutaneous Systemic Sclerosis Of Recent Onset., Fabian A. Mendoza, Md, Sarah J. Nagle, Jason B. Lee, Md, Sergio A. Jimenez

Jefferson Institute of Molecular Medicine Papers and Presentations

OBJECTIVE: A prospective observational study of mycophenolate mofetil (MMF) treatment in patients with diffuse progressive cutaneous systemic sclerosis (SSc) of recent onset.

METHODS: Twenty-five previously untreated consecutive patients with recent-onset (< 24 mo) diffuse progressive cutaneous SSc received MMF as the only disease-modifying therapy. Modified Rodnan skin score (mRSS) and affected body surface area (BSA) were compared from initiation of MMF to study end. Pulmonary function tests performed at the same institution before therapy and at study end were available in 15 patients. Histopathology and real-time PCR assessment of fibrosis-related gene expression were performed before and after treatment in skin biopsies from 3 patients.

RESULTS: At 18.2 ± 8.73 months of MMF therapy (median 2000 mg/day) the mRSS decreased from 24.56 ± 8.62 to 14.52 ± 10.9 (p = 0.0004) and the affected BSA from 36% ± 16% to 14% ± 13.3% (p = 0.00001). Pulmonary function tests remained stable from initiation of MMF to the end of the study. Skin histopathology showed a remarkable reduction in accumulation of fibrotic tissue. Real-time PCR …

Effects Of Immune Complexes From Sle Patients On Human Monocyte Locomotion And Fc Receptor Function, Katalin Lukacs, Maria Kavai, Aniko Banyai, Ildiko Sonkoly, Eva Vegh, Gyongyi Szabo, Gyula Szegedi

Gyongyi Szabo

The effect of immune complexes (IC) isolated from systemic lupus erythematosus (SLE) sera with polyethylene glycol and gel filtration on the chemotaxis and Fc receptor function of healthy monocytes was examined. Even at a low protein concentration (1 microgram/ml = 1 mg/l) ICs inhibit monocyte chemotaxis. ICs from patients with SLE nephritis are more inhibitory than ICs from patients without renal disease. The inhibitory effects of ICs on monocyte chemotaxis and Fc receptor activity are similar, suggesting a relationship between the chemotactic and Fc receptor function of monocytes. Analysis of the ICs by enzyme-linked immunoassay showed no correlation between the …

Acute Ethanol Treatment Augments Interleukin-12 Production In Activated Human Monocytes, Gyongyi Szabo, Linda Girouard, Pranoti Mandrekar, Donna Catalano

Gyongyi Szabo

No abstract provided.

Acute Alcohol Activates Stat3, Ap-1, And Sp-1 Transcription Factors Via The Family Of Src Kinases To Promote Il-10 Production In Human Monocytes, Oxana Norkina, Angela Dolganiuc, Taryn Shapiro, Karen Kodys, Pranoti Mandrekar, Gyongyi Szabo

Gyongyi Szabo

Alcohol consumption is associated with an imbalance in pro- and anti-inflammatory cytokines and immunosuppression, partially as a result of enhanced IL-10 production. The mechanisms of IL-10 induction by alcohol remain poorly understood. We identified that increased IL-10 production in human monocytes after acute in vivo alcohol consumption or in vitro alcohol treatment was associated with increased STAT3 activation. Alcohol alone induced and in combination with LPS augmented STAT3 phosphorylation at tyrosine 705 (tyr705) and serine 727 (ser727) residues and increased STAT3 binding to DNA. Upstream, alcohol activated the Src kinases, as indicated by an increase in phosphorylated and a decrease …

Regulation Of Human Monocyte Functions By Acute Ethanol Treatment: Decreased Tumor Necrosis Factor-Alpha, Interleukin-1 Beta And Elevated Interleukin-10, And Transforming Growth Factor-Beta Production, Gyongyi Szabo, Pranoti Mandrekar, Linda Girouard, Donna Catalano

Gyongyi Szabo

We and others have previously shown that even acute ethanol exposure has the capacity to modulate immune functions, particularly monocyte functions. Herein, we tested the hypothesis that acute ethanol treatment inhibits inflammatory, while increasing inhibitory cytokine production in human blood monocytes that, in turn, could contribute to the overall immune abnormalities seen after alcohol use. Our data show that in vitro treatment of blood monocytes with a physiologically relevant dose of alcohol (25 mM) results in significantly decreased induction of tumor necrosis factor-alpha (TNF alpha) and interleukin (IL)-1 beta by bacterial stimulation of either Gram-positive [staphylococcal enterotoxin B (SEB), 1 …

Acute Alcohol Consumption Attenuates Interleukin-8 (Il-8) And Monocyte Chemoattractant Peptide-1 (Mcp-1) Induction In Response To Ex Vivo Stimulation, Gyongyi Szabo, Sangeeta Chavan, Pranoti Mandrekar, Donna Catalano

Gyongyi Szabo

No abstract provided.

Regulation Of Monocyte Interleukin-12 Production By Acute Alcohol: A Role For Inhibition By Interleukin-10, Linda Girouard, Pranoti Mandrekar, Donna Catalano, Gyongyi Szabo

Gyongyi Szabo

Acute ethanol treatment results in decreased antigen presentation capacity (Th1-type immunity) and elevated interleukin IL-10 (Th2 cytokine) production in human monocytes. Monocytes can contribute to both Th1 (IL-12) and Th2 (IL-10) immune responses via production of IL-12 and IL-10, respectively. Thus, we tested the hypothesis that acute alcohol treatment might affect Th1/Th2 immune balance by altering monocyte production of IL-12 and IL-10. Neither acute ethanol treatment alone (25 to 100 mM) nor its combination with a bacterial challenge Staphylococcal enterotoxin B (SEB) induced IL-12 production in isolated blood monocytes. In contrast, the same physiological alcohol concentrations increased monocyte IL-10 levels, …

Pattern Recognition Receptors: A Contemporary View On Liver Diseases, Gyongyi Szabo, Angela Dolganiuc, Pranoti Mandrekar

Gyongyi Szabo

Pattern recognition receptors (PRRs) function as sensors of microbial danger signals enabling the vertebrate host to initiate an immune response. PRRs are present not only in immune cells but also in liver parenchymal cells and the complexity of the cell populations provide unique aspects to pathogen recognition and tissue damage in the liver. This review discusses the role of different PRRs in pathogen recognition in the liver, and focuses on the role of PRRs in hepatic inflammation, cholestasis, ischemia, repair and fibrosis. PRRs as novel therapeutic targets are evaluated.

Regulation Of Monocyte Il-12 Production: Augmentation By Lymphocyte Contact And Acute Ethanol Treatment, Inhibition By Elevated Intracellular Camp, Gyongyi Szabo, Linda Girouard, Pranoti Mandrekar, Donna Catalano

Gyongyi Szabo

IL-12, a monocyte-derived cytokine, is pivotal in activation of cellular immune response and inflammation. Both inflammatory response and cellular immunity are impaired by acute ethanol consumption. Here, we found that in vitro acute ethanol treatment (25-100 mM) results in a dose-dependent and significant increase of IL-12 in IFN-gamma (100 U/ml) plus Staphylococcal enterotoxin B (SEB; 1 microg/ml) stimulated monocytes and mononuclear cells but not in unstimulated cells from non-alcoholic blood donors. There was significantly greater IL-12 production in the MNC population compared to isolated Mphi (P < 0.001). Prevention of monocyte surface contact with either purified T lymphocytes or monocyte-depleted MNC resulted in a significant, 65+/-20%, decrease in IL-12 production regardless of IFN-gamma, SEB or ethanol stimulation suggesting that Mphi T-cell surface contact provides an additional signal for IL-12 production. In addition to cell surface contact, soluble mediators, particularly IL-10 and PGE2 may regulate IL-12 production. The cyclooxygenase inhibitor, Indomethacin (10(-6)M), augmented both IL-12 and IL-10 levels in isolated monocytes and mononuclear cells whether induced by medium, SEB or SEB plus 25 mM ethanol suggesting that regulation of IL-12 production via the cyclooxygenase pathway is independent of IL-10. Finally, elevation of intracellular cAMP levels by dbcAMP treatment consistently inhibited IL-12 as well as IL-10 production in monocytes induced by IFN-gamma or IFN-gamma plus 25 mM ethanol. These data suggest that augmentation of monocyte IL-12 by acute ethanol is not mediated via the cAMP pathway.

Ethanol-Mediated Regulation Of Transcription Factors In Immunocompetent Cells, Gyongyi Szabo, Pranoti Mandrekar

Gyongyi Szabo

The immunomodulatory effects of acute and chronic alcohol use are characterized by impaired antigen-specific immune activation and by increased susceptibility to infections due to alterations in innate immune responses and inflammatory mediator production. The central feature of cellular responses to inflammatory and stress signals is the activation of the nuclear regulatory kappa B/Rel family of transcriptional factors via various surface receptor systems in immunocompetent cells. Activation of NF-kappa B, however, is regulated at multiple levels including I-kappa B degradation, nuclear translocation, and by interaction of NF-kappa B/Rel with other transcription factors. Data from our and other laboratories demonstrate that acute …

Additive Inhibition Of Dendritic Cell Allostimulatory Capacity By Alcohol And Hepatitis C Is Not Restored By Dc Maturation And Involves Abnormal Il-10 And Il-2 Induction, Angela Dolganiuc, Karen Kodys, Andrea Kopasz, Christopher Marshall, Pranoti Mandrekar, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND: Excessive alcohol use results in impaired immunity, and it is associated with increased incidence and progression of chronic hepatitis C virus (HCV) infection. Here we investigated the effects of HCV infection and alcohol on myeloid dendritic cells (DC) that are critical in antiviral immunity.

METHODS: Immature and mature DCs were generated from monocytes of chronic HCV infected patients (HCV-DC) and controls (N-DC) with IL-4 plus granulocyte-macrophage colony stimulating factor (GM-CSF) in the presence or absence of alcohol (25 mM). DC allostimulatory capacity was tested in mixed lymphocyte reaction (MLR) and cytokine production by ELISA.

RESULTS: Allostimulatory capacity of HCV-DCs …

Acute Ethanol Treatment Modulates Toll-Like Receptor-4 Association With Lipid Rafts, Angela Dolganiuc, Genadyi Bakis, Karen Kodys, Pranoti Mandrekar, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND: Alcohol, a substance that is most frequently abused, suppresses innate immune responses to microbial pathogens. The host senses pathogens via Toll-like receptors (TLRs). Recent studies indicate that alcohol affects TLR signaling. METHODS: Here, we hypothesized that acute alcohol treatment may interfere with early steps of membrane-associated TLR2 and TLR4 signaling at the level of lipid rafts. Human monocytes and Chinese hamster ovary (CHO) cells, transfected with human TLR2, TLR4, or CD14, were stimulated with peptidoglycan (PGN, TLR2 ligand) or lipopolysaccharide (LPS, TLR4 ligand) with or without alcohol (50 mM) and analyzed for cytokine production (enzyme-linked immunosorbent assay), nuclear factor-kappaB …

Inhibition Of Lipopolysaccharide-Mediated Nfkappab Activation By Ethanol In Human Monocytes, Pranoti Mandrekar, Donna Catalano, Gyongyi Szabo

Gyongyi Szabo

Alcohol use is typically associated with impaired immunity and increased host susceptibility to infection, partially due to decreased inflammatory response. Acute ethanol exposure has been shown to down-regulate monocyte production of inflammatory cytokines. Activation of the pluripotent transcription factor NFkappaB is a pivotal step in the induction of inflammatory cytokines, chemokines and growth factors. Therefore, we hypothesized that alcohol may alter NFkappaB activation, thus providing a mechanism for the decreased inflammatory cytokine production by monocytes after acute alcohol treatment. We show here for the first time that alcohol inhibits lipopolysaccharide (LPS)-induced NFkappaB activation in human monocytes by decreasing DNA binding …

A Functional Difficulty And Functional Pain Instrument For Hip And Knee Osteoarthritis, Alan M. Jette, Christine M. Mcdonough, Pengsheng Ni, Stephen M. Haley

Dartmouth Scholarship

The objectives of this study were to develop a functional outcome instrument for hip and knee osteoarthritis research (OA-FUNCTION-CAT) using item response theory (IRT) and computer adaptive test (CAT) methods and to assess its psychometric performance compared to the current standard in the field.

Development And Validation Of An Index Of Musculoskeletal Functional Limitations, Jeffrey N. Katz, Elizabeth A. Wright, John A. Baron, Elena Losina

Dartmouth Scholarship

While musculoskeletal problems are leading sources of disability, there has been little research on measuring the number of functionally limiting musculoskeletal problems for use as predictor of outcome in studies of chronic disease. This paper reports on the development and preliminary validation of a self administered musculoskeletal functional limitations index.

Retinoid X Receptor And Peroxisome Proliferator-Activated Receptor-Gamma Agonists Cooperate To Inhibit Matrix Metalloproteinase Gene Expression, Peter S. Burrage, Adam C. Schmucker, Yanqing Ren, Michael B. Sporn, Constance E. Brinckerhoff

Dartmouth Scholarship

We recently described the ability of retinoid X receptor (RXR) ligand LG100268 (LG268) to inhibit interleukin-1-beta (IL-1-β)-driven matrix metalloproteinase-1 (MMP-1) and MMP-13 gene expression in SW-1353 chondrosarcoma cells. Other investigators have demonstrated similar effects in chondrocytes treated with rosiglitazone, a ligand for peroxisome proliferator-activated receptor-gamma (PPARγ), for which RXR is an obligate dimerization partner. The goals of this study were to evaluate the inhibition of IL-1--induced expression of MMP-1andMMP-13 by combinatorial treatment with RXR and PPAR  ligands and to investigate the molecular mechanisms of this inhibition.

Decreased Expression Of Caveolin 1 In Patients With Systemic Sclerosis: Crucial Role In The Pathogenesis Of Tissue Fibrosis., Francesco Del Galdo, Federica Sotgia, Cecilia J. De Almeida, Jean-Francois Jasmin, Megan Musick, Michael P. Lisanti, Sergio A. Jimenez

Department of Medicine Faculty Papers

OBJECTIVE: Recent studies have implicated caveolin 1 in the regulation of transforming growth factor beta (TGFbeta) downstream signaling. Given the crucial role of TGFbeta in the pathogenesis of systemic sclerosis (SSc), we sought to determine whether caveolin 1 is also involved in the pathogenesis of tissue fibrosis in SSc. We analyzed the expression of CAV1 in affected SSc tissues, studied the effects of lack of expression of CAV1 in vitro and in vivo, and analyzed the effects of restoration of caveolin 1 function on the fibrotic phenotype of SSc fibroblasts in vitro.

METHODS: CAV1 expression in tissues was analyzed by …

Molecular Ablation Of Transforming Growth Factor Beta Signaling Pathways By Tyrosine Kinase Inhibition: The Coming Of A Promising New Era In The Treatment Of Tissue Fibrosis., Joel Rosenbloom, Sergio A. Jimenez

Department of Medicine Faculty Papers

No abstract provided.

Modulation Of Tgf-Beta Signaling By Proinflammatory Cytokines In Articular Chondrocytes., Jorge A. Roman-Blas, David G. Stokes, Sergio A. Jimenez

Department of Medicine Faculty Papers

OBJECTIVE: The normal structure and function of articular cartilage are the result of a precisely balanced interaction between anabolic and catabolic processes. The transforming growth factor-beta (TGF-beta) family of growth factors generally exerts an anabolic or repair response; in contrast, proinflammatory cytokines such as interleukin 1 beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) exert a strong catabolic effect. Recent evidence has shown that IL-1beta, and TNF-alpha, and the TGF-beta signaling pathways share an antagonistic relationship. The aim of this study was to determine whether the modulation of the response of articular chondrocytes to TGF-beta by IL-1beta or TNF-alpha signaling pathways …