Osteopontin is increased in cystic fibrosis and can skew the functional balance between ELR-positive and ELR-negative CXC-chemokines Sandra Jovic, Medya.

Slides:

Advertisements

Similar presentations

Novel Role of Toll-Like Receptor 3 in Hepatitis C-Associated Glomerulonephritis Markus Wörnle, Holger Schmid, Bernhard Banas, Monika Merkle, Anna Henger,

Advertisements

MicroRNA-558 regulates the expression of cyclooxygenase-2 and IL-1β-induced catabolic effects in human articular chondrocytes S.J. Park, E.J. Cheon,

Novel Functional Single Nucleotide Polymorphisms in the Latent Transforming Growth Factor-β Binding Protein-1L Promoter Tomomi Higashi, Satoru Kyo, Masaki.

Azithromycin fails to reduce increased expression of neutrophil-related cytokines in primary-cultured epithelial cells from cystic fibrosis mice Ximena.

Serum matrix metalloproteinases in adult CF patients: Relation to pulmonary exacerbation Martin Roderfeld, Timo Rath, Richard Schulz, Werner Seeger,

Monocyte chemoattractant chemokines in cystic fibrosis

Neil E. Alexis, Marianne S. Muhlebach, David B. Peden, Terry L. Noah

Evaluation of a systems biology approach to identify pharmacological correctors of the mutant CFTR chloride channel Emanuela Pesce, Giulia Gorrieri,

The RD1-encoded antigen Rv3872 of Mycobacterium tuberculosis as a potential candidate for serodiagnosis of tuberculosis P. Mukherjee, M. Dutta, P. Datta,

Angiogenic effects of stromal cell-derived factor-1 (SDF-1/CXCL12) variants in vitro and the in vivo expressions of CXCL12 variants and CXCR4 in human.

Staphylococcus aureus Stimulates Neutrophil Targeting Chemokine Expression in Keratinocytes through an Autocrine IL-1α Signaling Loop Florina Olaru,

Identification of outer membrane Porin D as a vitronectin-binding factor in cystic fibrosis clinical isolates of Pseudomonas aeruginosa Magnus Paulsson,

MMP and non-MMP-mediated release of aggrecan and its fragments from articular cartilage: a comparative study of three different aggrecan and glycosaminoglycan.

Immunomodulatory activity of vardenafil on induced lung inflammation in cystic fibrosis mice Bob Lubamba, François Huaux, Jean Lebacq, Etienne Marbaix,

IL-22 exacerbates weight loss in a murine model of chronic pulmonary Pseudomonas aeruginosa infection Hannah K. Bayes, Neil D. Ritchie, Christopher Ward,

A novel neutrophil derived inflammatory biomarker of pulmonary exacerbation in cystic fibrosis Emer P. Reeves, David A. Bergin, Sean Fitzgerald, Elaine.

Role of IL-9 in the pathophysiology of allergic diseases

Yihan Wang, Michael A. Shia, Thomas G. Christensen, Steven C. Borkan

Anna L. P. Chapman, Brian M. Morrissey, Vihas T. Vasu, Maya M

MicroRNA-558 regulates the expression of cyclooxygenase-2 and IL-1β-induced catabolic effects in human articular chondrocytes S.J. Park, E.J. Cheon,

Kinetic Analysis of High Affinity Forms of Interleukin (IL)-13 Receptors: Suppression of IL-13 Binding by IL-2 Receptor γ Chain Vladimir A. Kuznetsov,

A small molecule neutrophil elastase inhibitor, KRP-109, inhibits cystic fibrosis mucin degradation Shashi Chillappagari, Christian Müller, Poornima.

Cell migration in response to the amino-terminal fragment of urokinase requires epidermal growth factor receptor activation through an ADAM-mediated mechanism

Glyoxalase I Is Differentially Expressed in Cutaneous Neoplasms and Contributes to the Progression of Squamous Cell Carcinoma Xiao-Yan Zou, Dong Ding,

Development of a quantitative immunofluorescence assay for detection of Stenotrophomonas maltophilia antibodies in patients with cystic fibrosis P. Gonçalves.

Impact of storage conditions on metabolite profiles of sputum samples from persons with cystic fibrosis Jiangchao Zhao, Charles R. Evans, Lisa A. Carmody,

Pseudomonas aeruginosa in cystic fibrosis: Pyocyanin negative strains are associated with BPI-ANCA and progressive lung disease Malin Carlsson, Swati.

Xu Shi-wen, Christopher P. Denton, Alan M. Holmes, Carol M

Innate immunity in cystic fibrosis lung disease

Therapeutic benefit observed with the CFTR potentiator, ivacaftor, in a CF patient homozygous for the W1282X CFTR nonsense mutation Venkateshwar Mutyam,

Toll-Like Receptor-Mediated Upregulation of CXCL16 in Psoriasis Orchestrates Neutrophil Activation Sabine Steffen, Susanne Abraham, Maik Herbig, Franziska.

Andrew J. Ghio, Victor L. Roggli, Joleen M. Soukup, Judy H

17β-estradiol, Progesterone, and Dihydrotestosterone Suppress the Growth of Human Melanoma by Inhibiting Interleukin-8 Production Naoko Kanda, Shinichi.

Raphaël Chiron, Y. Yaël Grumbach, Nga V. T

Osteopontin Expression Correlates with Melanoma Invasion

Inflammation in cystic fibrosis lung disease: Pathogenesis and therapy

Katelyn Krivchenia, Don Hayes, Joseph D. Tobias, Dmitry Tumin

Lung transplantation in patients with cystic fibrosis and Mycobacterium abscessus infection Marita Gilljam, Henrik Scherstén, Martin Silverborn, Bodil.

Ibuprofen rescues mutant cystic fibrosis transmembrane conductance regulator trafficking Graeme W. Carlile, Renaud Robert, Julie Goepp, Elizabeth Matthes,

Increased serum concentration of G-CSF in cystic fibrosis patients with chronic Pseudomonas aeruginosa pneumonia P.Ø. Jensen, C. Moser, A. Kharazmi,

Juliana I. Sesma, Bryant Wu, Timothy J. Stuhlmiller, David W. Scott

Amanda L. Brennan, Khin M. Gyi, David M

Bronchial epithelial cell lines and primary nasal epithelial cells from cystic fibrosis respond differently to cigarette smoke exposure Mark Thomas Shaw.

Fiona K. Dunlevy, S. Lorraine Martin, Francine de Courcey, J

Acute effects of viral respiratory tract infections on sputum bacterial density during CF pulmonary exacerbations Melanie Chin, Maya De Zoysa, Robert.

Role of Matriptase and Proteinase-Activated Receptor-2 in Nonmelanoma Skin Cancer Georgeta Bocheva, Anke Rattenholl, Cordula Kempkes, Tobias Goerge, Chen-Yong.

Lucas R. Hoffman, Hemantha D. Kulasekara, Julia Emerson, Laura S

Advanced glycation end products are elevated in cystic fibrosis-related diabetes and correlate with worse lung function William R. Hunt, Beth R. Helfman,

Pertussis Toxin-sensitive Secretory Phospholipase A2 Expression and Motility in Activated Primary Human Keratinocytes Krystyna E. Rys-Sikora, Alice P.

Comparison of real time diagnostic chemistries to detect Pseudomonas aeruginosa in respiratory samples from cystic fibrosis patients J.L. Fothergill,

Early inflammation in the airways of a cystic fibrosis foetus

Reassessment of the importance of mucins in determining sputum properties in cystic fibrosis Alex Horsley, Karine Rousseau, Caroline Ridley, William.

P. aeruginosa drives CXCL8 synthesis via redundant toll-like receptors and NADPH oxidase in CFTR∆F508 airway epithelial cells Lucie Roussel, Guy Martel,

Vitamin A and lung function in CF

Molecular analysis of changes in Pseudomonas aeruginosa load during treatment of a pulmonary exacerbation in cystic fibrosis D.W. Reid, R. Latham, I.L.

E. Tschiedel, H. Grasemann, F. Ratjen Journal of Cystic Fibrosis

Inhibition of ADAMTS-7 and ADAMTS-12 degradation of cartilage oligomeric matrix protein by alpha-2-macroglobulin Y. Luan, Ph.D., M.D., L. Kong, Ph.D.,

Novel concepts in evaluating antimicrobial therapy for bacterial lung infections in patients with cystic fibrosis Geraint B. Rogers, Lucas R. Hoffman,

Imre Szabo, Michele A. Wetzel, Thomas J. Rogers

Stability of interleukin 8 and neutrophil elastase in bronchoalveolar lavage fluid following long-term storage Luke J. Berry, Barbara Sheil, Luke Garratt,

Soluble inflammation markers in nasal lavage from CF patients and healthy controls Natalie Beiersdorf, Matthias Schien, Julia Hentschel, Wolfgang Pfister,

J.E. Spahr, R.B. Love, M. Francois, K. Radford, K.C. Meyer

Daniel J. Smith, Gregory J. Anderson, Scott C. Bell, David W. Reid

C. R. Hansen, T. Pressler, K. G. Nielsen, P. Ø. Jensen, T

Autoantibodies to BP180 Associated with Bullous Pemphigoid Release Interleukin-6 and Interleukin-8 from Cultured Human Keratinocytes Enno Schmidt, Stanislaus.

Airway inflammation in mild cystic fibrosis

Aluminum is a weak agonist for the calcium-sensing receptor

Elisabeth P. Dellon, Margaret W. Leigh, James R. Yankaskas, Terry L

Bcl-2 and bcl-xL Antisense Oligonucleotides Induce Apoptosis in Melanoma Cells of Different Clinical Stages Robert A. Olie, Christoph Hafner, Renzo Küttel,

Mark I. Block, MD The Annals of Thoracic Surgery

Presentation transcript:

Osteopontin is increased in cystic fibrosis and can skew the functional balance between ELR-positive and ELR-negative CXC-chemokines Sandra Jovic, Medya Shikhagaie, Matthias Mörgelin, Jonas S. Erjefält, Sven Kjellström, Arne Egesten Journal of Cystic Fibrosis Volume 14, Issue 4, Pages 453-463 (July 2015) DOI: 10.1016/j.jcf.2014.11.010 Copyright © 2014 European Cystic Fibrosis Society. Terms and Conditions

Fig. 1 Enhanced expression of OPN in the airways of CF patients. Immunohistochemistry to detect OPN was performed on lung tissue obtained from individuals undergoing lung transplantation for end stage CF (A–C; bar=100μm) or donors undergoing surgery for lung cancer (controls) (D–F). Using morphometric analysis, significantly less OPN was detected intra-epithelially of control lung tissue compared to CF lung tissue (G). Using an ELISA, OPN was quantified in sputum of CF patients, at a mean concentration of 2735pg/mL (range: 892–8170pg/mL; n=26) and in induced sputum from healthy controls, at a mean concentration of 53pg/mL (range 45–63pg/mL; n=3) (H). Mann–Whitney's U-test for unpaired samples was used for comparison between the groups. A P-value of less than 0.05 was considered significant (*P<0.05; ***P<0.001). Journal of Cystic Fibrosis 2015 14, 453-463DOI: (10.1016/j.jcf.2014.11.010) Copyright © 2014 European Cystic Fibrosis Society. Terms and Conditions

Fig. 2 Polymers and fragments of OPN in CF sputum. Western blot was performed to detect OPN in CF sputum and in induced sputum from healthy controls. Full length OPN was detected at approximately 65kDa (asterisk). In induced sputum from healthy controls (individuals 1–3), weak presence of OPN was seen. However, in CF sputum (individuals 4 and 5) strong presence of full length monomeric OPN (asterisk), numerous OPN-fragments and polymeric OPN was seen. In vitro, elastase of P. aeruginosa (PE) and neutrophil elastase (NE) released fragments of similar sizes as detected in CF sputum (arrows and arrowhead respectively) (A). The OPN fragment generated by PE (VSS) is derived from the mid-portion of OPN as indicated in blue, and the NE generated OPN fragment (LNA) is derived from the N-terminal portion of OPN as indicated in yellow (B). The biophysical properties of OPN and the fragments are shown (C). Journal of Cystic Fibrosis 2015 14, 453-463DOI: (10.1016/j.jcf.2014.11.010) Copyright © 2014 European Cystic Fibrosis Society. Terms and Conditions

Fig. 3 Binding of OPN to CXC-chemokines. Surface plasmon resonance analysis of OPN binding to CXC-chemokines. The strongest binding was measured between MIG/CXCL9 and OPN (KD=113nM) followed by I-TAC/CXCL11 and OPN (KD=1842nM) while IP-10/CXCL10 had a weaker binding to OPN (KD=15,060nM). Interestingly, no binding was observed between GRO-β/CXCL2, GCP-2/CXCL6, IL-8/CXCL8 and OPN (A). The enzyme-linked binding-assay confirmed the results obtained using surface plasmon resonance. However, a low binding between GRO-β/CXCL2, GCP-2/CXCL6, IL-8/CXCL8 and OPN was observed (B). Scanning electron microscopy (SEM) was performed to investigate the morphology of P. aeruginosa after incubation in buffer alone, with MIG/CXCL9 (1μM) conjugated with 5nm colloidal gold, or with MIG/CXCL9 pre-incubated with OPN (1μM) conjugated with 10nm colloidal gold (C). One representative out of three separate experiments is shown. Journal of Cystic Fibrosis 2015 14, 453-463DOI: (10.1016/j.jcf.2014.11.010) Copyright © 2014 European Cystic Fibrosis Society. Terms and Conditions

Fig. 3 Binding of OPN to CXC-chemokines. Surface plasmon resonance analysis of OPN binding to CXC-chemokines. The strongest binding was measured between MIG/CXCL9 and OPN (KD=113nM) followed by I-TAC/CXCL11 and OPN (KD=1842nM) while IP-10/CXCL10 had a weaker binding to OPN (KD=15,060nM). Interestingly, no binding was observed between GRO-β/CXCL2, GCP-2/CXCL6, IL-8/CXCL8 and OPN (A). The enzyme-linked binding-assay confirmed the results obtained using surface plasmon resonance. However, a low binding between GRO-β/CXCL2, GCP-2/CXCL6, IL-8/CXCL8 and OPN was observed (B). Scanning electron microscopy (SEM) was performed to investigate the morphology of P. aeruginosa after incubation in buffer alone, with MIG/CXCL9 (1μM) conjugated with 5nm colloidal gold, or with MIG/CXCL9 pre-incubated with OPN (1μM) conjugated with 10nm colloidal gold (C). One representative out of three separate experiments is shown. Journal of Cystic Fibrosis 2015 14, 453-463DOI: (10.1016/j.jcf.2014.11.010) Copyright © 2014 European Cystic Fibrosis Society. Terms and Conditions

Fig. 4 OPN inhibits the antibacterial activity of ELR-negative chemokines. MIG/CXCL9, IP-10/CXCL10, and I-TAC/CXCL11 (1μM) alone showed high bacterial killing. After pre-incubation with OPN at equimolar concentrations or at a ration of 1:0.1, the antibacterial activities of the chemokines were significantly reduced (A). The two elastase derived OPN-fragments, VSS and LNA did not reduce the bactericidal activity of MIG/CXCL9, IP-10/CXCL10 and I-TAC/CXCL11 to the same extent as the full-length protein did (B and C respectively). Mann–Whitney's U-test for unpaired samples was used for comparison between the groups. A P-value of less than 0.05 was considered significant (*P<0.05; **P<0.01; ***P<0.001). Journal of Cystic Fibrosis 2015 14, 453-463DOI: (10.1016/j.jcf.2014.11.010) Copyright © 2014 European Cystic Fibrosis Society. Terms and Conditions

Fig. 5 OPN interferes with activation of CXCR3-bearing cells but not neutrophils. MIG/CXCL9 IP-10/CXCL10, and I-TAC/CXCL11 (100nM) alone or pre-incubated with OPN (100nM) were investigated for their calcium-mobilizing properties in CXCR3-transfected cells (A). Likewise, GRO-β/CXCL2, GCP-2/CXCL6, and IL-8/CXCL8 alone and pre-incubated with OPN were investigated for intracellular calcium-mobilization in purified neutrophils (B). One representative and the mean and SD of three separate experiments respectively are shown. Unpaired t-test followed by Welch's correction was used for comparison between the groups. A P-value of less than 0.05 was considered significant (*P<0.05). Journal of Cystic Fibrosis 2015 14, 453-463DOI: (10.1016/j.jcf.2014.11.010) Copyright © 2014 European Cystic Fibrosis Society. Terms and Conditions