scholarly journals Distribution of airway smooth muscle remodelling in asthma: Relation to airway inflammation

Respirology ◽  
2014 ◽  
Vol 20 (1) ◽  
pp. 66-72 ◽  
Author(s):  
John G. Elliot ◽  
Robyn L. Jones ◽  
Michael J. Abramson ◽  
Francis H. Green ◽  
Thais Mauad ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Inflammation ◽  
Airway Smooth Muscle ◽  
Muscle Remodelling

Animal models of airway inflammation and airway smooth muscle remodelling in asthma

2009 ◽  
Vol 22 (5) ◽  
pp. 455-465 ◽  
Author(s):  
Judith E. Allen ◽  
Robert J. Bischof ◽  
Herng-Yu Sucie Chang ◽  
Jeremy A. Hirota ◽  
Stuart J. Hirst ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Animal Models ◽  
Airway Inflammation ◽  
Airway Smooth Muscle ◽  
Muscle Remodelling

scholarly journals Pro-inflammatory cytokines induce c-fos expression followed by IL-6 release in human airway smooth muscle cells

2001 ◽  
Vol 10 (3) ◽  
pp. 135-142 ◽  
Author(s):  
Sue McKay ◽  
Mechteld M. Grootte Bromhaar ◽  
Johan C. de Jongste ◽  
Henk C. Hoogsteden ◽  
Pramod R. Saxena ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Airway Inflammation ◽  
Conditioned Medium ◽  
Airway Smooth Muscle ◽  
Inflammatory Cytokines ◽  
Cell Counting ◽  
Airway Smooth Muscle Cells ◽  
Fos Expression ◽  
Pro Inflammatory Cytokines

Background: Airway smooth muscle (ASM) is considered to be a target for mediators released during airway inflammation.Aims: To investigate the expression of c-fos, a constituent of the transcription factor activator protein-1, in human ASM cells. In addition, to measure the release of interleukin (IL)-6 into the conditioned medium of stimulated ASM cells, as well as DNA biosynthesis and changes in cell number.Methods: Serum-deprived human ASM cells in the G0/G1phase were stimulated with the pro-inflammatory cytokines; tumour necrosis factor-α, IL-1β, IL-5 and IL-6. The expression of mRNA encoding the proto-oncogene c-fos was measured by Northern blot analysis. Cell proliferation was assessed by {3H}-thymidine incorporation assays and cell counting, and IL-6 levels in cell-conditioned medium were measured by enzyme-linked immunosorbent assay.Results: All of the cytokines investigated induced a rapid (within 1h) and transient increase in the expression of mRNA encoding c-fos, followed by the expression and enhanced release of IL-6. Cell proliferation remained unchanged in cytokine-stimulated cells.Conclusions: Cytokine-induced c-fos expression in human ASM cells could be described as a marker of cell ‘activation'. The possible association of these results with airway inflammation, through secondary intracellular mechanisms such as cytokine production, is discussed.

scholarly journals Airway smooth muscle proliferation and inflammation in asthma

2018 ◽  
Vol 125 (4) ◽  
pp. 1090-1096 ◽  
Author(s):  
Alan L. James ◽  
Peter B. Noble ◽  
Su-Ann Drew ◽  
Thais Mauad ◽  
Tony R. Bai ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Smooth Muscle Cell ◽  
Airway Inflammation ◽  
Cell Size ◽  
Airway Smooth Muscle ◽  
Muscle Cell ◽  
Muscle Cells ◽  
Muscle Layer ◽  
Airway Smooth Muscle Cells

In asthma, it is unclear if the airway smooth muscle cells proliferate more or are increased at the onset of asthma and remain stable. This study aimed to compare smooth muscle cell proliferation in individuals with and without asthma and correlate proliferation rates with cell size and number and with granulocytic airway inflammation. Postmortem airway sections were labeled with proliferating cell nuclear antigen (PCNA) and percent positive muscle cells calculated. On the same sections, smooth muscle cell size and number and the number of eosinophils and neutrophils were estimated and compared in cases of nonfatal ( n = 15) and fatal ( n = 15) asthma and control subjects ( n = 15). The %PCNA+ muscle cells was not significantly different in fatal (29.4 ± 7.7%, mean ± SD), nonfatal asthma (28.6 ± 8.3%), or control subjects (24.6 ± 6.7%) and not related to mean muscle cell size ( r = 0.09), number ( r = 0.36), thickness of the muscle layer ( r = 0.05), or eosinophil numbers ( r = 0.04) in the asthma cases. These data support the hypothesis that in asthma the increased thickness of the smooth muscle layer may be present before or at the onset of asthma and independent of concurrent granulocytic inflammation or exacerbation. NEW & NOTEWORTHY There is debate regarding the origins of the increased airway smooth muscle in asthma. It may be independent of inflammation or arise as a proliferative response to inflammation. The present study found no increase in the proportion of proliferating smooth muscle cells in asthma and no relation of proliferation to numbers of airway smooth muscle cells or inflammation. These results support a stable increase in smooth muscle in asthma that is independent of airway inflammation.

scholarly journals Effect of proinflammatory cytokines on regulation of sarcoplasmic reticulum Ca2+ reuptake in human airway smooth muscle

2009 ◽  
Vol 297 (1) ◽  
pp. L26-L34 ◽  
Author(s):  
Venkatachalem Sathish ◽  
Michael A. Thompson ◽  
Jeffrey P. Bailey ◽  
Christina M. Pabelick ◽  
Y. S. Prakash ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Sarcoplasmic Reticulum ◽  
Airway Inflammation ◽  
Airway Smooth Muscle ◽  
Proinflammatory Cytokines ◽  
Cell Types ◽  
Human Airway Smooth Muscle ◽  
Inhibitory Protein ◽  
Intracellular Ca ◽  
Additional Exposure

Airway inflammation leads to increased intracellular Ca2+ ([Ca2+]i) levels in airway smooth muscle (ASM) cells. Sarcoplasmic reticulum Ca2+ release and reuptake are key components of ASM [Ca2+]i regulation. Ca2+ reuptake occurs via sarcoendoplasmic reticulum Ca2+ ATPase (SERCA) and is regulated by the inhibitory protein phospholamban (PLB) in many cell types. In human ASM, we tested the hypothesis that inflammation increases PLB, thus inhibiting SERCA function, and leading to maintained [Ca2+]i levels. Surprisingly, we found that human ASM does not express PLB protein (although mRNA is detectable). Overnight exposure to the proinflammatory cytokines TNFα and IL-13 did not induce PLB expression, raising the issue of how SERCA is regulated. We then found that direct SERCA phosphorylation (via CaMKII) occurs in human ASM. In fura-2-loaded human ASM cells, we found that the CaMKII antagonist KN-93 significantly slowed the rate of fall of [Ca2+]i transients induced by ACh or bradykinin (in zero extracellular Ca2+), suggesting a role for CaMKII-mediated SERCA regulation. SERCA expression was decreased by cytokine exposure, and the rate of fall of [Ca2+]i transients was slowed in cells exposed to TNFα and IL-13. Cytokine effects on Ca2+ reuptake were unaffected by additional exposure to KN-93. These data indicate that in human ASM, SERCA is regulated by mechanisms such as CaMKII and that airway inflammation maintains [Ca2+]i levels by decreasing SERCA expression and slowing Ca2+ reuptake.

Selected Contribution: Tryptase-induced PAR-2-mediated Ca2+signaling in human airway smooth muscle cells

2001 ◽  
Vol 91 (2) ◽  
pp. 995-1003 ◽  
Author(s):  
Patrick Berger ◽  
J. Manuel Tunon-De-Lara ◽  
Jean-Pierre Savineau ◽  
Roger Marthan
Keyword(s):  
Smooth Muscle ◽  
Airway Inflammation ◽  
Airway Smooth Muscle ◽  
Airway Smooth Muscle Cells ◽  
Atpase Inhibitor ◽  
Human Airway Smooth Muscle ◽  
Human Airway ◽  
Transient Rise ◽  
Intracellular Ca ◽  
Protein Kinase C Inhibitor

Tryptase, the major mast cell product, is considered to play an important role in airway inflammation and hyperresponsiveness. Tryptase produces different, sometimes opposite, effects on airway responsiveness (bronchoprotection and/or airway contraction). This study was designed to examine the effect of human lung tryptase and activation of protease-activated receptor (PAR)-2 by synthetic activated peptide (AP) SLIGKV-NH2 on Ca2+ signaling in human airway smooth muscle (HASM) cells. Immunocytochemistry revealed that PAR-2 was expressed by HASM cells. Tryptase (7.5–30 mU/ml) induced a concentration-dependent transient relative rise in cytoplasmic Ca2+ concentration ([Ca2+]i) that reached 207 ± 32 nM ( n = 10) measured by indo 1 spectrofluorometry. The protease inhibitors leupeptin or benzamidine (100 μM) abolished tryptase-induced [Ca2+]iincrease. Activation of PAR-2 by AP (1–100 μM) also induced a concentration-dependent transient rise in [Ca2+]i, whereas the reverse peptide produced no effect. There was a homologous desensitization of the [Ca2+]i response on repeated stimulation with tryptase or AP. U-73122, a specific phospholipase C (PLC) antagonist, xestospongin, an inositol trisphosphate (IP3)-receptor antagonist, or thapsigargin, a sarcoplamic Ca2+-ATPase inhibitor, abolished tryptase-induced [Ca2+]iresponse, whereas Ca2+ removal, in the additional presence of EGTA, had no effect. Calphostin C, a protein kinase C inhibitor, increased PAR-2 [Ca2+]i response. Our results indicate that tryptase activates a [Ca2+]iresponse, which appears as PAR-2 mediated in HASM cells. Signal transduction implicates the intracellular Ca2+ store via PLC activation and thus via the IP3 pathway. This study provides evidence that tryptase, which is increasingly recognized as an important mediator in airway inflammation and hyperresponsiveness, is also a potent direct agonist at the site of airway smooth muscle.

Acetylcholine: a novel regulator of airway smooth muscle remodelling?

2004 ◽  
Vol 500 (1-3) ◽  
pp. 193-201 ◽  
Author(s):  
Reinoud Gosens ◽  
Johan Zaagsma ◽  
Mechteld Grootte Bromhaar ◽  
Adriaan Nelemans ◽  
Herman Meurs
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Muscle Remodelling

scholarly journals Regulation of IL-17A and implications for TGF-β1 comodulation of airway smooth muscle remodeling in severe asthma

2019 ◽  
Vol 316 (5) ◽  
pp. L843-L868 ◽  
Author(s):  
Jon M. Evasovic ◽  
Cherie A. Singer
Keyword(s):  
Smooth Muscle ◽  
Airway Inflammation ◽  
Severe Asthma ◽  
Airway Smooth Muscle ◽  
Transforming Growth Factor ◽  
Airway Remodeling ◽  
High Dose ◽  
Persistent Symptoms ◽  
Immune Factors ◽  
Tgf Β1

Severe asthma develops as a result of heightened, persistent symptoms that generally coincide with pronounced neutrophilic airway inflammation. In individuals with severe asthma, symptoms are poorly controlled by high-dose inhaled glucocorticoids and often lead to elevated morbidity and mortality rates that underscore the necessity for novel drug target identification that overcomes limitations in disease management. Many incidences of severe asthma are mechanistically associated with T helper 17 (TH17) cell-derived cytokines and immune factors that mediate neutrophilic influx to the airways. TH17-secreted interleukin-17A (IL-17A) is an independent risk factor for severe asthma that impacts airway smooth muscle (ASM) remodeling. TH17-derived cytokines and diverse immune mediators further interact with structural cells of the airway to induce pathophysiological processes that impact ASM functionality. Transforming growth factor-β1 (TGF-β1) is a pivotal mediator involved in airway remodeling that correlates with enhanced TH17 activity in individuals with severe asthma and is essential to TH17 differentiation and IL-17A production. IL-17A can also reciprocally enhance activation of TGF-β1 signaling pathways, whereas combined TH1/TH17 or TH2/TH17 immune responses may additively impact asthma severity. This review seeks to provide a comprehensive summary of cytokine-driven T cell fate determination and TH17-mediated airway inflammation. It will further review the evidence demonstrating the extent to which IL-17A interacts with various immune factors, specifically TGF-β1, to contribute to ASM remodeling and altered function in TH17-driven endotypes of severe asthma.

Calpain-activated mTORC2/Akt pathway mediates airway smooth muscle remodelling in asthma

2016 ◽  
Vol 47 (2) ◽  
pp. 176-189 ◽  
Author(s):  
S.-S. Rao ◽  
Q. Mu ◽  
Y. Zeng ◽  
P.-C. Cai ◽  
F. Liu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Akt Pathway ◽  
Muscle Remodelling

scholarly journals Neonatal Streptococcus pneumoniae Pneumonia Induces an Aberrant Airway Smooth Muscle Phenotype and AHR in Mice Model

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Xin Peng ◽  
Yi Wu ◽  
Xiao Kong ◽  
Yunxiu Chen ◽  
Yonglu Tian ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Streptococcus Pneumoniae ◽  
Airway Inflammation ◽  
Allergic Asthma ◽  
Airway Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Inflammatory Cells ◽  
Pivotal Role ◽  
Mice Model ◽  
Asthma Model

Our previous study showed that neonatal S. pneumoniae infection aggravated airway inflammation and airway hyperresponsiveness (AHR) in an OVA-induced allergic asthma model. As airway smooth muscle (ASM) plays a pivotal role in AHR development, we aim to investigate the effects of neonatal S. pneumoniae pneumonia on ASM structure and AHR development. Non-lethal neonatal pneumonia was established by intranasally infecting 1-week-old BALB/C mice with the S. pneumoniae strain D39. Five weeks after infection, the lungs were collected to assess the levels of α-SMA and the contractile proteins of ASM. Our results indicate that neonatal S. pneumoniae pneumonia significantly increased adulthood lung α-SMA and SMMHC proteins production and aggravated airway inflammatory cells infiltration and cytokines release. In addition, the neonatal S. pneumoniae pneumonia group had significantly higher Penh values compared to the uninfected controls. These data suggest that neonatal S. pneumoniae pneumonia promoted an aberrant ASM phenotype and AHR development in mice model.

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