PFF Teal = 0+160+175 MAIN COLORS PFF Green = 120+162+47 Light Green = 193+216+47 Red = 242+102+73 HIGHLIGHT COLORS Light Grey = 220+220+210 Dark Grey =

Slides:



Advertisements
Similar presentations
Update in ILD: Current Approaches to IPF Andrew M. Tager, M.D.
Advertisements

Embryonic Stem Cell Research: Debate and Controversy Leigh Kemp.
A homo-dimer of annexin V protects against ischemia reperfusion injury in lung transplantation K Hashimoto, H Kim, H Oishi, M Chen, I Iskender, J Sakamoto,
The role of microfibrillar-associated protein 4 (MFAP4) in asthma Bartosz Pilecki PhD student Institute of Molecular Medicine University of Southern Denmark,
CHRONIC OBSTRUCTIVE PULMONARY DISEASE ZULEYHA OZEN.
IL-4 in TB Dr. Huang-Pin Wu Div. Pul. Med., Dep. Int. Med., Chang Gung Memorial Hospital, Keelung.
OXYGEN SENSING, HOMEOSTASIS, AND DISEASE SEMENZA. NEJM, AUGUST 2011, 246: 6 Amelia Crawford PA-S2.
G. S / AIH 2006 Graft-versus-Host disease Physiopathology Gérard Socié, MD PhD Hospital Saint Louis Translating experimental into clinical knowledge.
Cell Diversity The move from unicellular to multicellular organisms occurred through cell specialization. The division of required tasks necessary to maintain.
三重大学医学部病理 Deficiency of tenascin-C attenuates liver
PFF Teal = MAIN COLORS PFF Green = Light Green = Red = HIGHLIGHT COLORS Light Grey = Dark Grey =
PFF Teal = MAIN COLORS PFF Green = Light Green = Red = HIGHLIGHT COLORS Light Grey = Dark Grey =
Rachel G. Scheraga, MD Cleveland Clinic Cleveland, OH
PFF Teal = MAIN COLORS PFF Green = Light Green = Red = HIGHLIGHT COLORS Light Grey = Dark Grey =
PFF Teal = MAIN COLORS PFF Green = Light Green = Red = HIGHLIGHT COLORS Light Grey = Dark Grey =
PFF Teal = MAIN COLORS PFF Green = Light Green = Red = HIGHLIGHT COLORS Light Grey = Dark Grey =
PFF Teal = MAIN COLORS PFF Green = Light Green = Red = HIGHLIGHT COLORS Light Grey = Dark Grey =
PFF Teal = MAIN COLORS PFF Green = Light Green = Red = HIGHLIGHT COLORS Light Grey = Dark Grey =
PFF Teal = MAIN COLORS PFF Green = Light Green = Red = HIGHLIGHT COLORS Light Grey = Dark Grey =
PFF Teal = MAIN COLORS PFF Green = Light Green = Red = HIGHLIGHT COLORS Light Grey = Dark Grey =
PFF Teal = MAIN COLORS PFF Green = Light Green = Red = HIGHLIGHT COLORS Light Grey = Dark Grey =
PFF Teal = MAIN COLORS PFF Green = Light Green = Red = HIGHLIGHT COLORS Light Grey = Dark Grey =
PFF Teal = MAIN COLORS PFF Green = Light Green = Red = HIGHLIGHT COLORS Light Grey = Dark Grey =
PFF Teal = MAIN COLORS PFF Green = Light Green = Red = HIGHLIGHT COLORS Light Grey = Dark Grey =
PFF Teal = MAIN COLORS PFF Green = Light Green = Red = HIGHLIGHT COLORS Light Grey = Dark Grey =
PFF Teal = MAIN COLORS PFF Green = Light Green = Red = HIGHLIGHT COLORS Light Grey = Dark Grey =
SIRT3, the Anti-aging Major Mitochondrial Deacetylase, Is Important for Preventing Pulmonary Fibrosis Renea Jablonski, MD Kamp Lab November 14, 2015.
The role of microfibrillar-associated protein 4 (MFAP4) in asthma Bartosz Pilecki PhD student Institute of Molecular Medicine University of Southern Denmark,
PFF Teal = MAIN COLORS PFF Green = Light Green = Red = HIGHLIGHT COLORS Light Grey = Dark Grey =
PFF Teal = MAIN COLORS PFF Green = Light Green = Red = HIGHLIGHT COLORS Light Grey = Dark Grey =
R1 정수웅.  Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive, fibrosing interstitial pneumonia of unknown cause that occurs.
Adenosine Protects Vascular Barrier Function in Hyperoxic Lung Injury Jonathan Davies 1, Harry Karmouty-Quintana 2, Thuy T. Le 2, Ning-Yuan Chen 2, Tingting.
INTRODUCTION ABSENCE OF MAST CELLS IN AN EXPERIMENTAL MODEL OF PULMONARY AND CARDIAC FIBROSIS, THE CUX-1 MICE Navya A Reddy 1, Farhan Raza 1, Ahmed Said.
STEM CELL RESEARCH. What are stem cells? Cells that can generate more copies of themselves Have specialized function in body.
The role of regulatory B cells on hepatocellular carcinoma progression Conclusion Results Fig2. (A and B) In vivo, Bregs in SCID mice increased the size.
STEM CELL TREATMENT IN INDIA Why to chose stem cell treatment in India?
* * * * * * * Results Abstract Description of intervention/study
Strong reversal of the lung fibrosis disease signature by autotaxin inhibitor GLPG1690 in a mouse model for IPF Maté Ongenaert, PhD Senior Scientist Bioinformatics.
Proposed mechanism for the pathogenesis of pulmonary fibrosis
ΓδT Cell–Derived Interleukin-17A via an Interleukin-1β–Dependent Mechanism Mediates Cardiac Injury and Fibrosis in HypertensionNovelty and Significance.
Activation of NK cells during the early stage of allergic and fibrotic lung inflammation. Activation of NK cells during the early stage of allergic and.
Brown SMN1,2, Bush A1,2, Davies JC1,2, Thursfield R1,2, Lloyd CM1
Mary E. Huerter, MD, MA, Ashish K
Mariola Kurowska-Stolarska, PhD, Manhl K. Hasoo, PhD, David J
Volume 12, Issue 1, Pages (July 2005)
Volume 16, Issue 1, Pages (June 2016)
Atelectasis, acute respiratory distress syndrome & pulmonary edema
Representative images of immunohistochemical staining of discoidin domain receptor (DDR)2 in interstitial lung disease (ILD) other than idiopathic pulmonary.
Comparative expression of discoidin domain receptors (DDRs) between healthy lung tissues and those from different types of interstitial lung disease (ILD):
Elevated ecto-5′-nucleotidase: a missing pathogenic factor and new therapeutic target for sickle cell disease by Hong Liu, Morayo Adebiyi, Rong Rong Liu,
Fig. 5. Vascularization of human liver seed grafts.
Volume 140, Issue 2, Pages e4 (February 2011)
Volume 24, Issue 5, Pages (May 2016)
Alveolar lymphangiogenesis is a feature of idiopathic pulmonary fibrosis (IPF). a) Tissue sections reacted with anti-D2-40 (brown) and anti-CD34 (red)
Systems biology as a tool to improve idiopathic pulmonary fibrosis (IPF) treatment effectiveness. Systems biology as a tool to improve idiopathic pulmonary.
Bone marrow transplantation prevents right ventricle disease in the caveolin-1–deficient mouse model of pulmonary hypertension by Kewal Asosingh, Nicholas.
Proteinase activated receptor-1 expression in a) weak immunostaining in normal lung tissue, b) intense immunostaining in idiopathic pulmonary fibrosis,
Molecular factors involved in pulmonary fibrosis in fra-2tg mice.
UCN‐01 inhibits human IPF lung fibroblast pathological phenotypes and attenuates lung fibrosis induced by bleomycin injury UCN‐01 inhibits human IPF lung.
IL-10R-deficient macrophages secrete IL-23, inducing IL-22 secretion by ILC3 and TH17 cells. IL-10R-deficient macrophages secrete IL-23, inducing IL-22.
miR-29 Inhibits Bleomycin-induced Pulmonary Fibrosis in Mice
Loss of BAP1 blocks T cell differentiation at the DN3 stage in vitro.
The extra domain A of fibronectin is essential for allergen-induced airway fibrosis and hyperresponsiveness in mice  Martin Kohan, MSc, Andres F. Muro,
TH-302 has antileukemia activity in an in vivo primary AML xenograft murine model. TH-302 has antileukemia activity in an in vivo primary AML xenograft.
Type I collagen–targeted PET probe for pulmonary fibrosis detection and staging in preclinical models by Pauline Désogère, Luis F. Tapias, Lida P. Hariri,
Fig. 5. Vascularization of human liver seed grafts.
Advances and highlights in mechanisms of allergic disease in 2015
SY-1425 induces maturation in RARA-high AML
Treg expression of Gata3 plays a major role in controlling dermal fibrosis. Treg expression of Gata3 plays a major role in controlling dermal fibrosis.
Single-cell characterization of macrophages in fibrotic and regenerative microenvironments. Single-cell characterization of macrophages in fibrotic and.
Presentation transcript:

PFF Teal = MAIN COLORS PFF Green = Light Green = Red = HIGHLIGHT COLORS Light Grey = Dark Grey = Black = THE ROLE OF MACROPHAGES IN FIBROSIS MICHAEL R. BLACKBURN, PhD LUNG REMODELING AND REGENERATION FRIDAY NOVEMBER 13, 2015

PFF Teal = MAIN COLORS PFF Green = Light Green = Red = HIGHLIGHT COLORS Light Grey = Dark Grey = Black = THE DIVERSITY OF MACROPHAGES ©2015 Pulmonary Fibrosis Foundation. All rights reserved.2 web.mit.edu - generated in bone marrow - specialized function in tissues Brock, T.G. Cayman Chemicals - diverse activation and function in host defense and disease - roles in wound healing and tissue remodeling

PFF Teal = MAIN COLORS PFF Green = Light Green = Red = HIGHLIGHT COLORS Light Grey = Dark Grey = Black = MACROPHAGES IN FIBROSIS ©2015 Pulmonary Fibrosis Foundation. All rights reserved.3 CD206 Arg-1 AAM Wynn & Murray. Nature Medicine. Vol 18: (2012).

PFF Teal = MAIN COLORS PFF Green = Light Green = Red = HIGHLIGHT COLORS Light Grey = Dark Grey = Black = Adenosine Adenosine Receptors (A 1 R, A 2A R, A 2B R, A 3 R) Cell Injury Hypoxia Pro-InflammatoryAnti-Inflammatory ? (tissue destruction/remodeling) (pro-fibrotic) (tissue protection) (barrier function) (wound healing) ©2015 Pulmonary Fibrosis Foundation. All rights reserved.4 Hypothesis: Adenosine signaling is too much of a good thing in pulmonary fibrosis.

PFF Teal = MAIN COLORS PFF Green = Light Green = Red = HIGHLIGHT COLORS Light Grey = Dark Grey = Black = A 2B R Signaling - pro and anti-inflammatory features - widely distributed and induced following injury (hypoxia) - low affinity for adenosine - G  s - pro- and anti-fibrotic features Hypothesis: A 2B R signaling contributes to the progression of pulmonary fibrosis. - pro-fibrotic activities on pulmonary cells - elevated in patients with chronic lung disease - tissue protective (vascular/epithelial barrier function) ©2015 Pulmonary Fibrosis Foundation. All rights reserved.5

PFF Teal = MAIN COLORS PFF Green = Light Green = Red = HIGHLIGHT COLORS Light Grey = Dark Grey = Black = In Vivo Antagonism of the A 2B R in Mice Exposed to Bleomycin CVT-6883 aka GS-6201 ©2015 Pulmonary Fibrosis Foundation. All rights reserved.6 Day 1Day 15 Day33 Intra-peritoneal Bleomycin Fibrosis Hypertension CVT-6883/ GS-6201 GS-6201 Diet

PFF Teal = MAIN COLORS PFF Green = Light Green = Red = HIGHLIGHT COLORS Light Grey = Dark Grey = Black = A 2B R Antagonism in Bleomycin-Induced Lung Injury saline + CVT-6883 bleomycin + CVT-6883bleomycin + vehicle Sun et al. (2006) J. Clin. Invest. 116, 2173 ©2015 Pulmonary Fibrosis Foundation. All rights reserved.7

PFF Teal = MAIN COLORS PFF Green = Light Green = Red = HIGHLIGHT COLORS Light Grey = Dark Grey = Black = Reduced Bleomycin-Induced Lung Fibrosis in A 2B R Knockout Mice Zhou et al. (2011) J. Immunol. 186, 1097 ©2015 Pulmonary Fibrosis Foundation. All rights reserved.8

PFF Teal = MAIN COLORS PFF Green = Light Green = Red = HIGHLIGHT COLORS Light Grey = Dark Grey = Black = A 2B R Signaling and IL-6 Levels Induction of fibrotic genes ©2015 Pulmonary Fibrosis Foundation. All rights reserved.9

PFF Teal = MAIN COLORS PFF Green = Light Green = Red = HIGHLIGHT COLORS Light Grey = Dark Grey = Black = A2B-DEPENDENT EXPRESSION OF IL-6 ©2015 Pulmonary Fibrosis Foundation. All rights reserved. 10 Attenuated pulmonary fibrosis is associated with decreased IL-6 production in alveolar macrophages of A 2B R knockout mice. Zhou et al. (2011) J. Immunol. 186, 1097 ELISA Immunostain

PFF Teal = MAIN COLORS PFF Green = Light Green = Red = HIGHLIGHT COLORS Light Grey = Dark Grey = Black = A 2B R Signaling and Alternatively Activated (M2) Macrophages lavage cell pellets primary lung macrophage cultures ©2015 Pulmonary Fibrosis Foundation. All rights reserved. 11

PFF Teal = MAIN COLORS PFF Green = Light Green = Red = HIGHLIGHT COLORS Light Grey = Dark Grey = Black = DECREASED IL-6 IN A2B CONDITIONAL KNOCKOUT MICE ©2015 Pulmonary Fibrosis Foundation. All rights reserved. 12 Karmouty-Quintana et al. (2015) FASEB J. 29, 50

PFF Teal = MAIN COLORS PFF Green = Light Green = Red = HIGHLIGHT COLORS Light Grey = Dark Grey = Black = Karmouty-Quintana et al. (2015) FASEB J. 29, 50 ©2015 Pulmonary Fibrosis Foundation. All rights reserved. DECREASED FIBROSIS IN A2B CONDITIONAL KNOCKOUT MICE

PFF Teal = MAIN COLORS PFF Green = Light Green = Red = HIGHLIGHT COLORS Light Grey = Dark Grey = Black = A 2B R and IL-6 in IPF ©2015 Pulmonary Fibrosis Foundation. All rights reserved.14

PFF Teal = MAIN COLORS PFF Green = Light Green = Red = HIGHLIGHT COLORS Light Grey = Dark Grey = Black = A 2B R-Dependent Expression of IL-6 in IPF staining ©2015 Pulmonary Fibrosis Foundation. All rights reserved.15

PFF Teal = MAIN COLORS PFF Green = Light Green = Red = HIGHLIGHT COLORS Light Grey = Dark Grey = Black = GS-6201 primary macrophages from IPF patients CD206 A 2B R-Dependent Expression of IL-6 in IPF ©2015 Pulmonary Fibrosis Foundation. All rights reserved.16 - Potential approach for targeted response to A2B antagonist in clinical trials

PFF Teal = MAIN COLORS PFF Green = Light Green = Red = HIGHLIGHT COLORS Light Grey = Dark Grey = Black = Working Model ©2015 Pulmonary Fibrosis Foundation. All rights reserved A2B adenosine receptor is elevated on M2 cells - M2 A2B plays a role in IL-6 production a fibrosis - A2B antagonism attenuates active lung fibrosis - A2B is a potential target for IPF therapy - M2 macrophages are prevalent in lung fibrosis Conclusions

PFF Teal = MAIN COLORS PFF Green = Light Green = Red = HIGHLIGHT COLORS Light Grey = Dark Grey = Black = Jose Molina Dewan Zeng (Gilead Scientific) Luiz Belardinelli (Gilead Scientific) Thuy Le Funding Tingting Weng Hongyan Zhong (Gilead Scientific) Harry Karmouty-Quintana Blackburn Lab Collaborators Jonathan Davies Mathias Loebe Luis Garcia Raquel Bunge Brian Bruckner Methodist Hospital Ning Chen Holger Eltzschig (UC Denver) RO1-HL PO1-HL Jay Murthy (UTHealth) Richard Castriota (UTHealth) Soma Jyothula (UTHealth) Kemly Philips Frank Lou Kelly Volcik Yang Zhou Gilead National Heart, Lung, and Blood Institute