scholarly journals CD4+T cells enhance the unloaded shortening velocity of airway smooth muscle by altering the contractile protein expression

2014 ◽  
Vol 592 (14) ◽  
pp. 2999-3012 ◽  
Author(s):  
Oleg S. Matusovsky ◽  
Emily M. Nakada ◽  
Linda Kachmar ◽  
Elizabeth D. Fixman ◽  
Anne-Marie Lauzon
Keyword(s):  
T Cells ◽  
Smooth Muscle ◽  
Protein Expression ◽  
Airway Smooth Muscle ◽  
Cd4 T Cells ◽  
Contractile Protein ◽  
Shortening Velocity

Extracellular matrix proteins differentially regulate airway smooth muscle phenotype and function

2007 ◽  
Vol 292 (6) ◽  
pp. L1405-L1413 ◽  
Author(s):  
Bart G. J. Dekkers ◽  
Dedmer Schaafsma ◽  
S. Adriaan Nelemans ◽  
Johan Zaagsma ◽  
Herman Meurs
Keyword(s):  
Smooth Muscle ◽  
Protein Expression ◽  
Airway Smooth Muscle ◽  
Airway Remodeling ◽  
Negative Control ◽  
Collagen I ◽  
Contractile Protein ◽  
Chronic Obstructive ◽  
Ecm Proteins ◽  
And Function

Changes in the ECM and increased airway smooth muscle (ASM) mass are major contributors to airway remodeling in asthma and chronic obstructive pulmonary disease. It has recently been demonstrated that ECM proteins may differentially affect proliferation and expression of phenotypic markers of cultured ASM cells. In the present study, we investigated the functional relevance of ECM proteins in the modulation of ASM contractility using bovine tracheal smooth muscle (BTSM) preparations. The results demonstrate that culturing of BSTM strips for 4 days in the presence of fibronectin or collagen I depressed maximal contraction (Emax) both for methacholine and KCl, which was associated with decreased contractile protein expression. By contrast, both fibronectin and collagen I increased proliferation of cultured BTSM cells. Similar effects were observed for PDGF. Moreover, PDGF augmented fibronectin- and collagen I-induced proliferation in an additive fashion, without an additional effect on contractility or contractile protein expression. The fibronectin-induced depression of contractility was blocked by the integrin antagonist Arg-Gly-Asp-Ser (RGDS) but not by its negative control Gly-Arg-Ala-Asp-Ser-Pro (GRADSP). Laminin, by itself, did not affect contractility or proliferation but reduced the effects of PDGF on these parameters. Strong relationships were found between the ECM-induced changes in Emax in BTSM strips and their proliferative responses in BSTM cells and for Emax and contractile protein expression. Our results indicate that ECM proteins differentially regulate both phenotype and function of intact ASM.

scholarly journals Antigen-specific CD4+ T cells drive airway smooth muscle remodeling in experimental asthma

2005 ◽  
Vol 115 (6) ◽  
pp. 1580-1589 ◽  
Author(s):  
David Ramos-Barbón ◽  
John F. Presley ◽  
Qutayba A. Hamid ◽  
Elizabeth D. Fixman ◽  
James G. Martin
Keyword(s):  
T Cells ◽  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Cd4 T Cells ◽  
Muscle Remodeling

l-Thyroxine promotes a proliferative airway smooth muscle phenotype in the presence of TGF-β1

2015 ◽  
Vol 308 (3) ◽  
pp. L301-L306 ◽  
Author(s):  
Bart G. J. Dekkers ◽  
Saeideh Naeimi ◽  
I. Sophie T. Bos ◽  
Mark H. Menzen ◽  
Andrew J. Halayko ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Thyroid Hormones ◽  
Protein Expression ◽  
Airway Smooth Muscle ◽  
Transforming Growth Factor ◽  
Airway Remodeling ◽  
Contractile Protein ◽  
Cell Phenotype ◽  
Minor Effect ◽  
Tgf Β1

Hypothyroidism may reduce, whereas hyperthyroidism may aggravate, asthma symptoms. The mechanisms underlying this relationship are largely unknown. Since thyroid hormones have central roles in cell growth and differentiation, we hypothesized that airway remodeling, in particular increased airway smooth muscle (ASM) mass, may be involved. To address this hypothesis, we investigated the effects of triiodothyronine (T3) and l-thyroxine (T4) in the absence and presence of the profibrotic transforming growth factor (TGF)-β1 on human ASM cell phenotype switching. T3 (1–100 nM) and T4 (1–100 nM) did not affect basal ASM proliferation. However, when combined with TGF-β1 (2 ng/ml), T4 synergistically increased the proliferative response, whereas only a minor effect was observed for T3. In line with a switch from a contractile to a proliferative ASM phenotype, T4 reduced the TGF-β1-induced contractile protein expression by ∼50%. Cotreatment with T3 reduced TGF-β1-induced contractile protein expression by ∼25%. The synergistic increase in proliferation was almost fully inhibited by the integrin αvβ3 antagonist tetrac (100 nM), whereas no significant effects of the thyroid receptor antagonist 1–850 (3 μM) were observed. Inhibition of MEK1/2, downstream of the integrin αvβ3, also inhibited the T4- and TGF-β1-induced proliferative responses. Collectively, the results indicate that T4, and to a lesser extent T3, promotes a proliferative ASM phenotype in the presence of TGF-β1, which is predominantly mediated by the membrane-bound T4 receptor αvβ3. These results indicate that thyroid hormones may enhance ASM remodeling in asthma, which could be of relevance for hyperthyroid patients with this disease.

Muscarinic receptor stimulation augments TGF-β1-induced contractile protein expression by airway smooth muscle cells

2012 ◽  
Vol 303 (7) ◽  
pp. L589-L597 ◽  
Author(s):  
Tjitske A. Oenema ◽  
Marieke Smit ◽  
Lyanne Smedinga ◽  
Kurt Racké ◽  
Andrew J. Halayko ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Protein Expression ◽  
Muscarinic Receptor ◽  
Airway Smooth Muscle ◽  
Transforming Growth Factor ◽  
Glycogen Synthase ◽  
Airway Remodeling ◽  
Contractile Protein ◽  
Airway Smooth Muscle Cells ◽  
Receptor Stimulation

Acetylcholine (ACh) is the primary parasympathetic neurotransmitter in the airways. Recently, it was established that ACh, via muscarinic receptors, regulates airway remodeling in animal models of asthma and chronic obstructive pulmonary disease (COPD). The mechanisms involved are not well understood. Here, we investigated the functional interaction between muscarinic receptor stimulation and transforming growth factor (TGF)-β1 on the expression of contractile proteins in human airway smooth muscle (ASM) cells. ASM cells expressing functional muscarinic M2 and M3 receptors were stimulated with methacholine (MCh), TGF-β1, or their combination for up to 7 days. Western blot analysis revealed a strong induction of sm-α-actin and calponin by TGF-β1, which was increased by MCh in ASM cells. Immunocytochemistry confirmed these results and revealed that the presence of MCh augmented the formation of sm-α-actin stress fibers by TGF-β1. MCh did not augment TGF-β1-induced gene transcription of contractile phenotype markers. Rather, translational processes were involved in the augmentation of TGF-β1-induced contractile protein expression by muscarinic receptor stimulation, including phosphorylation of glycogen synthase kinase-3β and 4E-binding protein 1, which was enhanced by MCh. In conclusion, muscarinic receptor stimulation augments functional effects of TGF-β1 in human ASM cells on cellular processes that underpin ASM remodeling in asthma and COPD.

scholarly journals Nanotubes Connect CD4+T Cells to Airway Smooth Muscle Cells: Novel Mechanism of T Cell Survival

2015 ◽  
Vol 194 (12) ◽  
pp. 5626-5634 ◽  
Author(s):  
Saba Al Heialy ◽  
Melissa Zeroual ◽  
Soroor Farahnak ◽  
Toby McGovern ◽  
Paul-André Risse ◽  
...  
Keyword(s):  
T Cells ◽  
Smooth Muscle ◽  
T Cell ◽  
Smooth Muscle Cells ◽  
Cell Survival ◽  
Airway Smooth Muscle ◽  
Cd4 T Cells ◽  
Muscle Cells ◽  
Airway Smooth Muscle Cells ◽  
T Cell Survival

Regulation of airway smooth muscle α-actin expression by glucocorticoids

2007 ◽  
Vol 292 (1) ◽  
pp. L99-L106 ◽  
Author(s):  
Adam M. Goldsmith ◽  
Marc B. Hershenson ◽  
Miguel P. Wolbert ◽  
J. Kelley Bentley
Keyword(s):  
Smooth Muscle ◽  
Protein Expression ◽  
Airway Smooth Muscle ◽  
Contractile Function ◽  
Smooth Muscle Actin ◽  
Mrna Translation ◽  
Contractile Protein ◽  
Muscle Actin ◽  
Actin Expression ◽  
Actin Protein

Airway smooth muscle hypertrophy appears to be present in severe asthma. However, the effect of corticosteroids on airway smooth muscle cell size or contractile protein expression has not been studied. We examined the effects of dexamethasone, fluticasone, and salmeterol on contractile protein expression in transforming growth factor (TGF)-β-treated primary bronchial smooth muscle cells. Dexamethasone and fluticasone, but not salmeterol, each reduced expression of α-smooth muscle actin and the short isoform of myosin light chain kinase. Steady-state α-actin mRNA level and stability were unchanged, consistent with posttranscriptional control. Fluticasone significantly decreased α-actin protein synthesis following treatment with the transcriptional inhibitor actinomycin D, indicative of an inhibitory effect on mRNA translation. Fluticasone also significantly increased α-actin protein turnover. Finally, fluticasone reduced TGF-β-induced incorporation of α-actin into filamentous actin, cell length, and cell shortening in response to ACh and KCl. We conclude that glucocorticoids reduce human airway smooth muscle α-smooth muscle actin expression and incorporation into contractile filaments, as well as contractile function, in part by attenuation of mRNA translation and enhancement of protein degradation.

scholarly journals Interferons modulate mitogen-induced protein synthesis in airway smooth muscle

2010 ◽  
Vol 299 (1) ◽  
pp. L25-L35 ◽  
Author(s):  
Elena A. Goncharova ◽  
Poay N. Lim ◽  
Amelia Chisolm ◽  
Homer W. Fogle ◽  
Jerome H. Taylor ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Smooth Muscle ◽  
Cell Growth ◽  
Protein Expression ◽  
Cell Size ◽  
Airway Smooth Muscle ◽  
Contractile Protein ◽  
Combined Effects ◽  
Cytosolic Protein ◽  
Ifn Γ

Severe asthma is characterized by increased airway smooth muscle (ASM) mass due, in part, to ASM cell growth and contractile protein expression associated with increased protein synthesis. Little is known regarding the combined effects of mitogens and interferons on ASM cytosolic protein synthesis. We demonstrate that human ASM mitogens including PDGF, EGF, and thrombin stimulate protein synthesis. Surprisingly, pleiotropic cytokines IFN-β and IFN-γ, which inhibit ASM proliferation, also increased cytosolic protein content in ASM cells. Thus IFN-β alone significantly increased protein synthesis by 1.62 ± 0.09-fold that was further enhanced by EGF to 2.52 ± 0.17-fold. IFN-γ alone also stimulated protein synthesis by 1.91 ± 0.15-fold; treatment of cells with PDGF, EGF, and thrombin in the presence of IFN-γ stimulated protein synthesis by 2.24 ± 0.3-, 1.25 ± 0.17-, and 2.67 ± 0.34-fold, respectively, compared with growth factors alone. The mammalian target of rapamycin (mTOR)/S6 kinase 1 (S6K1) inhibition with rapamycin inhibited IFN- and EGF-induced protein synthesis, suggesting that IFN-induced protein synthesis is modulated by mTOR/S6K1 activation. Furthermore, overexpression of tumor suppressor protein tuberous sclerosis complex 2 (TSC2), which is an upstream negative regulator of mTOR/S6K1 signaling, also inhibited mitogen-induced protein synthesis in ASM cells. IFN-β and IFN-γ stimulated miR143/145 microRNA expression and increased SM α-actin accumulation but had little effect on ASM cell size. In contrast, EGF increased ASM cell size but had little effect on miR143/145 expression. Our data demonstrate that both IFNs and mitogens stimulate protein synthesis but have differential effects on cell size and contractile protein expression and suggest that combined effects of IFNs and mitogens may contribute to ASM cell growth, contractile protein expression, and ASM remodeling in asthma.

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