Fibroblast Radiosensitivity In Vitro and Lung Fibrosis In Vivo: Comparison between a Fibrosis-Prone and Fibrosis-Resistant Mouse Strain

1996 ◽  
Vol 146 (1) ◽  
pp. 61 ◽  
Author(s):  
Christine L. Dileto ◽  
Elizabeth L. Travis
Keyword(s):  
Mouse Strain ◽  
Lung Fibrosis ◽  
Resistant Mouse ◽  
Resistant Mouse Strain

scholarly journals Connective tissue growth factor mRNA expression is upregulated in bleomycin-induced lung fibrosis

1998 ◽  
Vol 275 (2) ◽  
pp. L365-L371 ◽  
Author(s):  
Joseph A. Lasky ◽  
Luis A. Ortiz ◽  
Boihoang Tonthat ◽  
Gary W. Hoyle ◽  
Miriam Corti ◽  
...  
Keyword(s):  
Growth Factor ◽  
Connective Tissue ◽  
Mouse Strain ◽  
Lung Fibrosis ◽  
Tissue Growth ◽  
Lung Fibroblasts ◽  
Resistant Mouse ◽  
Tgf Β1 ◽  
Resistant Mouse Strain

Connective tissue growth factor (CTGF) is a newly described 38-kDa peptide mitogen for fibroblasts and a promoter of connective tissue deposition in the skin. The CTGF gene promotor contains a transforming growth factor-β1 (TGF-β1) response element. Because TGF-β1 expression is upregulated in several models of fibroproliferative lung disease, we asked whether CTGF is also upregulated in a murine lung fibrosis model and whether CTGF could mediate some of the fibrogenic effects associated with TGF-β1. A portion of the rat CTGF gene was cloned and used to show that primary isolates of both murine and human lung fibroblasts express CTGF mRNA in vitro. There was a greater than twofold increase in CTGF expression in both human and murine lung fibroblasts 2, 4, and 24 h after the addition of TGF-β1 in vitro. A bleomycin-sensitive mouse strain (C57BL/6) and a bleomycin-resistant mouse strain (BALB/c) were given bleomycin, a known lung fibrogenic agent. CTGF mRNA expression was upregulated in the sensitive, but not in the resistant, mouse strain after administration of bleomycin. In vivo differences in the CTGF expression between the two mouse strains were not due to an inherent inability of BALB/c lung fibroblasts to respond to TGF-β1 because fibroblasts from untreated BALB/c mouse lung upregulated their CTGF message when treated with TGF-β1 in vitro. These data demonstrate that CTGF is expressed in lung fibroblasts and may play a role in the pathogenesis of lung fibrosis.

Mouse Strain Differences in in vivo and in vitro Immunosuppressive Effects of Opioids

1995 ◽  
pp. 115-121 ◽  
Author(s):  
Toby K. Eisenstein ◽  
Joseph J. Meissler ◽  
Jeanine L. Bussiere ◽  
Thomas J. Rogers ◽  
Ellen B. Geller ◽  
...  
Keyword(s):  
Mouse Strain ◽  
Strain Differences ◽  
Mouse Strain Differences

scholarly journals Novel EGFRvIII-CAR transgenic mice for rigorous preclinical studies in syngeneic mice

2021 ◽  
Author(s):  
Pavlina Chuntova ◽  
Yafei Hou ◽  
Ryosuke Naka ◽  
Yitzhar Goretsky ◽  
Takahide Nejo ◽  
...  
Keyword(s):  
T Cells ◽  
Mouse Strain ◽  
Growth Factor Receptor ◽  
Suppressor Cells ◽  
Cytotoxic Activities ◽  
Combination Regimen ◽  
Preclinical Studies ◽  
Term Survival

ABSTRACTBackgroundRigorous preclinical studies of chimeric antigen receptor (CAR) immunotherapy will require large quantities of consistent and high-quality CAR-transduced T (CART)-cells that can be used in syngeneic mouse glioblastoma (GBM) models. To this end, we developed a novel transgenic (Tg) mouse strain with a fully murinized CAR targeting epidermal growth factor receptor variant III (EGFRvIII).MethodsWe first established the murinized version of EGFRvIII-CAR and validated its function using a retroviral vector (RV) in C57BL/6J mice bearing syngeneic SB28 GBM expressing EGFRvIII. Next, we created C57BL/6J-background Tg mice carrying the anti-EGFRvIII-CAR downstream of a Lox-Stop-Lox cassette in the Rosa26 locus. We bred these mice with CD4-Cre Tg mice to allow CAR expression on T-cells and evaluated the function of the CART-cells both in vitro and in vivo. In order to inhibit immunosuppressive myeloid cells within SB28 GBM, we also evaluated a combination approach of CART and an anti-EP4 compound (ONO-AE3-208).ResultsBoth RV- and Tg-CART-cells demonstrated specific cytotoxic activities against SB28-EGFRvIII cells. A single intravenous infusion of EGFRvIII-CART-cells prolonged the survival of glioma-bearing mice when preceded by a lymphodepletion regimen with recurrent tumors displaying profound EGFRvIII loss. The addition of ONO-AE3-208 resulted in long-term survival in a fraction of CART-treated mice and those survivors demonstrated delayed growth of subcutaneously re-challenged both EGFRvIII+ and parental EGFRvIII− SB28.ConclusionOur new syngeneic CAR Tg mouse model can serve as a useful tool to address clinically relevant questions and develop future immunotherapeutic strategies.Importance of studyThe majority of preclinical studies evaluating CART therapy for GBM have utilized xenografts implanted into immunocompromised mice. Because the successful development of these strategies will depend on the understanding of critical interactions between therapeutic cells and the endogenous immune environment, it is essential to develop a novel immunocompetent system which allows us to study these interactions in a robust and reproducible manner. To this end, we created a Tg mouse strain in which all T-cells express a murinized EGFRvIII-CAR. T-cells derived from these mice demonstrated consistent CAR expression and EGFRvIII-specific cytotoxicity while traditional transduction with a CAR vector showed batch-to-batch variability. The syngeneic system also gave us the opportunity to evaluate a combination regimen with blockade of myeloid-derived suppressor cells. The Tg-CART mice represent a novel system for robust, and reproducible preclinical investigations.

Fucoxanthin inhibits profibrotic protein expression in vitro and attenuates bleomycin-induced lung fibrosis in vivo

2017 ◽  
Vol 811 ◽  
pp. 199-207 ◽  
Author(s):  
Sun Young Ma ◽  
Won Sun Park ◽  
Dae-Sung Lee ◽  
Grace Choi ◽  
Mi-Jin Yim ◽  
...  
Keyword(s):  
Protein Expression ◽  
Lung Fibrosis

Antifibrotic properties of caveolin-1 scaffolding domain in vitro and in vivo

2008 ◽  
Vol 294 (5) ◽  
pp. L843-L861 ◽  
Author(s):  
Elena Tourkina ◽  
Mathieu Richard ◽  
Pal Gööz ◽  
Michael Bonner ◽  
Jaspreet Pannu ◽  
...  
Keyword(s):  
Lung Fibrosis ◽  
Smooth Muscle Actin ◽  
Lung Fibroblasts ◽  
Normal Lung ◽  
Signaling Molecule ◽  
Caveolin 1 ◽  
Tenascin C ◽  
Ecm Proteins

Lung fibrosis involves the overexpression of ECM proteins, primarily collagen, by α-smooth muscle actin (ASMA)-positive cells. Caveolin-1 is a master regulator of collagen expression by cultured lung fibroblasts and of lung fibrosis in vivo. A peptide equivalent to the caveolin-1 scaffolding domain (CSD peptide) inhibits collagen and tenascin-C expression by normal lung fibroblasts (NLF) and fibroblasts from the fibrotic lungs of scleroderma patients (SLF). CSD peptide inhibits ASMA expression in SLF but not NLF. Similar inhibition of collagen, tenascin-C, and ASMA expression was also observed when caveolin-1 expression was upregulated using adenovirus. These observations suggest that the low caveolin-1 levels in SLF cause their overexpression of collagen, tenascin-C, and ASMA. In mechanistic studies, MEK, ERK, JNK, and Akt were hyperactivated in SLF, and CSD peptide inhibited their activation and altered their subcellular localization. These studies and experiments using kinase inhibitors suggest many differences between NLF and SLF in signaling cascades. To validate these data, we determined that the alterations in signaling molecule activation observed in SLF also occur in fibrotic lung tissue from scleroderma patients and in mice with bleomycin-induced lung fibrosis. Finally, we demonstrated that systemic administration of CSD peptide to bleomycin-treated mice blocks epithelial cell apoptosis, inflammatory cell infiltration, and changes in tissue morphology as well as signaling molecule activation and collagen, tenascin-C, and ASMA expression associated with lung fibrosis. CSD peptide may be a prototype for novel treatments for human lung fibrosis that act, in part, by inhibiting the expression of ASMA and ECM proteins.

Paradoxical increase in LDL oxidation by endothelial cells from an atherosclerosis-resistant mouse strain

2007 ◽  
Vol 192 (2) ◽  
pp. 259-265 ◽  
Author(s):  
Toru Miyoshi ◽  
Alan H. Matsumoto ◽  
Weibin Shi
Keyword(s):  
Endothelial Cells ◽  
Mouse Strain ◽  
Ldl Oxidation ◽  
Resistant Mouse ◽  
Resistant Mouse Strain

scholarly journals Atherosclerosis Susceptibility Loci Identified in an Extremely Atherosclerosis‐Resistant Mouse Strain

2013 ◽  
Vol 2 (4) ◽  
Author(s):  
Jessica S. Rowlan ◽  
Qiongzhen Li ◽  
Ani Manichaikul ◽  
Qian Wang ◽  
Alan H. Matsumoto ◽  
...  
Keyword(s):  
Mouse Strain ◽  
Susceptibility Loci ◽  
Resistant Mouse ◽  
Resistant Mouse Strain

scholarly journals Methylation-mediated BMPER expression in fibroblast activation in vitro and lung fibrosis in mice in vivo

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Caijuan Huan ◽  
Ting Yang ◽  
Jiurong Liang ◽  
Ting Xie ◽  
Luis Cheng ◽  
...  
Keyword(s):  
Lung Fibrosis ◽  
Fibroblast Activation
Sign in / Sign up

Export Citation Format

Share Document