Contribution of Upregulated Airway Endothelin-1 Expression to Airway Smooth Muscle and Epithelial Cell DNA Synthesis after Repeated Allergen Exposure of Sensitized Brown-Norway Rats

2000 ◽  
Vol 23 (5) ◽  
pp. 618-625 ◽  
Author(s):  
Michael Salmon ◽  
Yu-Chih Liu ◽  
Judith C. W. Mak ◽  
Jonathan Rousell ◽  
Tung-Jung Huang ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Epithelial Cell ◽  
Dna Synthesis ◽  
Airway Smooth Muscle ◽  
Allergen Exposure ◽  
Brown Norway ◽  
Endothelin 1 ◽  
Norway Rats

scholarly journals Repeated allergen inhalations induce DNA synthesis in airway smooth muscle and epithelial cells in vivo

1998 ◽  
Vol 274 (3) ◽  
pp. L417-L424 ◽  
Author(s):  
Reynold A. Panettieri ◽  
Richard K. Murray ◽  
Andrew J. Eszterhas ◽  
Gulsevil Bilgen ◽  
James G. Martin
Keyword(s):  
Smooth Muscle ◽  
Epithelial Cells ◽  
Basement Membrane ◽  
Dna Synthesis ◽  
Airway Smooth Muscle ◽  
Allergen Challenge ◽  
Brown Norway ◽  
Small Airways ◽  
Airway Epithelial

Airway smooth muscle (ASM) mass appears to be increased in the bronchi of patients with chronic severe asthma. Although the precise mechanisms that induce these changes are unknown, increases in ASM mass are caused, in part, by ASM cell proliferation. After allergen challenge in rats, it has been possible to demonstrate an increase in ASM mass by morphometric techniques. To examine whether hyperplasia is involved in ASM cell growth in vivo, we investigated whether repeated allergen challenges in sensitized Brown Norway rats stimulated DNA synthesis in airway epithelial and ASM cells. Animals that were actively sensitized to ovalbumin (OA) received either three aerosolized OA or saline challenges at 5-day intervals. DNA synthesis was measured by indirect immunohistochemical techniques with an anti-bromodeoxyuridine (BrdU) antibody. OA inhalations increased ASM mass as determined by morphometry and also induced DNA synthesis in both airway epithelial and ASM cells in the airways of sensitized animals compared with saline-challenged control animals. ASM mass was increased in large- and medium-sized airways but not in small airways. However, the number of BrdU-positive ASM cells normalized to basement membrane length was also greater in the large- and medium-sized airways compared with that in the small airways. When the number of BrdU-positive epithelial cells was normalized to basement membrane length, there was no difference among airway sizes and the number of BrdU-positive epithelial cells. These data suggest that DNA synthesis is induced in both airway epithelial and ASM cells after inhalational antigen challenge.

scholarly journals Effects of Zileuton on Airway Smooth Muscle Remodeling after Repeated Allergen Challenge in Brown Norway Rats

Respiration ◽  
2013 ◽  
Vol 86 (5) ◽  
pp. 421-429 ◽  
Author(s):  
Wei-Ji Chen ◽  
Shwu-Fang Liaw ◽  
Ching-Chi Lin ◽  
Mei-Wei Lin ◽  
Feng-Ting Chang
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Allergen Challenge ◽  
Brown Norway ◽  
Norway Rats ◽  
Muscle Remodeling

scholarly journals Repeated allergen exposure of sensitized Brown-Norway rats induces airway cell DNA synthesis and remodelling

1999 ◽  
Vol 14 (3) ◽  
pp. 633 ◽  
Author(s):  
M. Salmon ◽  
D.a. Walsh ◽  
H Koto ◽  
P.j Barnes ◽  
K.f Chung
Keyword(s):  
Dna Synthesis ◽  
Allergen Exposure ◽  
Brown Norway ◽  
Norway Rats

Actin reorganization in airway smooth muscle cells involves Gq and Gi-2 activation of Rho

1999 ◽  
Vol 277 (3) ◽  
pp. L653-L661 ◽  
Author(s):  
Carol A. Hirshman ◽  
Charles W. Emala
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Airway Smooth Muscle ◽  
Actin Polymerization ◽  
Muscle Cells ◽  
Fiber Formation ◽  
Airway Smooth Muscle Cells ◽  
Actin Reorganization ◽  
Endothelin 1 ◽  
In Cells

Extracellular stimuli induce cytoskeleton reorganization (stress-fiber formation) in cells and Ca2+ sensitization in intact smooth muscle preparations by activating signaling pathways that involve Rho proteins, a subfamily of the Ras superfamily of monomeric G proteins. In airway smooth muscle, the agonists responsible for cytoskeletal reorganization via actin polymerization are poorly understood. Carbachol-, lysophosphatidic acid (LPA)-, and endothelin-1-induced increases in filamentous actin staining are indicative of actin reorganization (filamentous-to-globular actin ratios of 2.4 ± 0.3 in control cells, 6.7 ± 0.8 with carbachol, 7.2 ± 0.8 with LPA, and 7.4 ± 0.9 with endothelin-1; P < 0.001; n = 14 experiments). Although the effect of all agonists was blocked by C3 exoenzyme (inactivator of Rho), only carbachol was blocked by pertussis toxin. Although carbachol-induced actin reorganization was blocked in cells pretreated with antisense oligonucleotides directed against Gαi-2 alone, LPA- and endothelin-1-induced actin reorganization were only blocked when both Gαi-2 and Gqα were depleted. These data indicate that in human airway smooth muscle cells, carbachol induces actin reorganization via a Gαi-2pathway, whereas LPA or endothelin-1 induce actin reorganization via either a Gαi-2 or a Gqα pathway.

Epithelial Modulation of Airway Smooth Muscle Response to Endothelin-1

1991 ◽  
Vol 144 (2) ◽  
pp. 373-378 ◽  
Author(s):  
Steven R. White ◽  
Darren P. Hathaway ◽  
Jason G. Umans ◽  
Julio Tallet ◽  
Cyril Abrahams ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Muscle Response ◽  
Endothelin 1

Heparin and PGE2 inhibit DNA synthesis in human airway smooth muscle cells in culture

1995 ◽  
Vol 269 (4) ◽  
pp. L514-L519 ◽  
Author(s):  
P. R. Johnson ◽  
C. L. Armour ◽  
D. Carey ◽  
J. L. Black
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Dna Synthesis ◽  
Airway Smooth Muscle ◽  
Muscle Cells ◽  
Airway Smooth Muscle Cells ◽  
Human Airway Smooth Muscle ◽  
Cells In Culture ◽  
Human Airway ◽  
Inhibition Of Dna Synthesis

An increase in the bulk of the airway smooth muscle is a characteristic of asthma. Much of the research investigating the mechanisms of this increase in muscle has focused on mediators that are mitogenic for smooth muscle, while relatively few studies have focused on mediators inhibiting mitogenesis. In this study we have examined the effects of two mediators proposed as regulators of smooth muscle proliferation, namely heparin and prostaglandin (PG) E2, on human airway smooth muscle cells in culture stimulated with 1, 2.5, 5, and 10% fetal bovine serum (FBS) and platelet-derived growth factor AB (PDGF), 50 ng/ml. PGE2 had a biphasic effect on DNA synthesis in the presence of 1% FBS, with 10(-6) M causing inhibition and 10(-7) M causing an increase in DNA synthesis. PGE2 caused inhibition of DNA synthesis in the presence of 2.5, 5, and 10% FBS. Heparin (10 and 100 U/ml) caused an inhibition of DNA synthesis induced by 1% FBS, while 100 U/ml inhibited DNA synthesis induced by 5 and 10% FBS. PGE2 (10(-8), 10(-7), and 10(-6) M) inhibited the DNA synthesis induced by PDGF, while heparin (1, 10, and 100 U/ml) had no effect. These results indicate that both PGE2 and heparin may have a role in the control of human airway smooth muscle cell growth.

Treatment with a sphingosine-1-phosphate analog inhibits airway remodeling following repeated allergen exposure

2012 ◽  
Vol 302 (8) ◽  
pp. L736-L745 ◽  
Author(s):  
Harry Karmouty-Quintana ◽  
Sana Siddiqui ◽  
Muhannad Hassan ◽  
Kimitake Tsuchiya ◽  
Paul-Andre Risse ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Severe Asthma ◽  
Airway Smooth Muscle ◽  
Airway Remodeling ◽  
Allergic Inflammation ◽  
Allergen Challenge ◽  
Allergen Exposure ◽  
Lipid Mediator ◽  
Synthetic Analog ◽  
Sphingosine 1 Phosphate

Sphingosine-1-phosphate (S1P) is an immunomodulatory lipid mediator that plays an important role in lymphocyte trafficking. Elevated levels of S1P are found in bronchoalveolar lavage (BAL) fluid of patients with asthma; however, its role in disease is not known. FTY720, a synthetic analog of S1P, has been shown to abrogate allergic inflammation and airway hyperresponsiveness following acute allergen challenge. However, its effects on asthmatic airway remodeling induced by repeated allergen exposure are unknown. Ovalbumin (OVA)-sensitized rats were challenged on days 14, 19, and 24 after sensitization. FTY720 or vehicle (PBS) therapy was administered 1 h prior to each challenge. BAL fluid and quantitative histological analysis were performed 48 h after the last challenge. FTY720 inhibited OVA-induced features of airway remodeling including increased airway smooth muscle mass and bronchial neovascularization, without affecting lymphocyte numbers in secondary lymphoid organs. Furthermore, CD3+ cells adjacent to airway smooth muscle bundles were increased in OVA-challenged rats but the increase was inhibited by FTY720. There was an expansion of bronchus-associated lymphoid tissue following FTY720 treatment of OVA-challenged animals. Real-time quantitative PCR revealed that Th2-associated transcription factors were inhibited following FTY720 therapy. Airway remodeling is a cardinal feature of severe asthma. These results demonstrate that allergen-driven airway remodeling can be inhibited by FTY720, offering potential new therapies for the treatment of severe asthma.

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