Salbutamol inhibits the proliferation of human airway smooth muscle cells grown in culture: Relationship to elevated cAMP levels

Tomlinson, Paul R.; Wilson, John W.; Stewart, Alastair G.

doi:10.1016/0006-2952(94)00532-q

Cited by 99 publications

(57 citation statements)

References 39 publications

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“…The action of b 2 -adrenoceptor agonists is considered to be dependent largely on increases in intracellular cyclic adenosine monophosphate (AMP) levels, consistent with the antiproliferative effect of agents which directly increase cyclic AMP levels [158]. In another study, STEWART et al [159] recently demonstrated that the b 2 -adrenoceptor agonist, salbutamol, opposes the passage of human airway smooth muscle cells through the cell cycle restriction point.…”

Section: Role Of Phosphoinositide 3-kinase Activation In Proliferationmentioning

confidence: 95%

Phenotypic diversity and molecular mechanisms of airway smooth muscle proliferation in asthma

Hirst¹,

Walker²,

Chilvers³

2000

Eur Respir J

109

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Chronic persistent asthma is characterized by poorly reversible airflow obstruction and airways inflammation and remodelling. Histopathological studies of airways removed at post mortem from patients with severe asthma reveal marked inflammatory and architectural changes associated with airway wall thickening. Increased airway smooth muscle content, occurring as a result of hyperplastic and/or hypertrophic growth, is believed to be one of the principal contributors to airway wall thickening. In recent years, significant advances have been made in elucidating the mediators and the intracellular pathways that regulate proliferation of airway smooth muscle. The contribution that smooth muscle makes to persistent airflow obstruction may not, however, be limited simply to its increased bulk within the airway wall. Interest is growing in the possibility that reversible phenotypic modulation and increased heterogeneity of airway smooth muscle function may also be a feature of the asthmatic airway. This review focuses on possible mechanisms controlling smooth muscle phenotype heterogeneity as well as on the mediators and intracellular pathways implicated in its cellular proliferation. Particular attention is paid to mechanisms involving activation of the extracellular signal regulated kinase‐, protein kinase C‐ and phosphoinositide 3‐kinase‐dependent pathways, since these appear to be the major candidate second messenger pathways for G protein‐ and tyrosine kinase‐coupled receptor‐stimulated proliferation.

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Section: Role Of Phosphoinositide 3-kinase Activation In Proliferationmentioning

confidence: 95%

Phenotypic diversity and molecular mechanisms of airway smooth muscle proliferation in asthma

Hirst¹,

Walker²,

Chilvers³

2000

Eur Respir J

109

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“…Increases in intracellular cAMP, brought about by agents that activate adenylyl cyclase or by cAMP analogues that activate PKA, have been reported to induce apoptosis and/or inhibit proliferation in some cells, including lymphoid cells (41)(42)(43)(44), granulosa cells (45), tumor cells (46 -48), and cultured smooth muscle cells (49). PDE inhibitors, by presumably increasing cAMP, have also been reported to inhibit proliferation/induce apoptosis of lymphoid cells (50 -53), cultured vascular smooth muscle cells (54), and tumor cells (55).…”

Section: Effects Of Pde Inhibitors and Camp On Bad Phosphorylation Anmentioning

confidence: 99%

Cyclic Nucleotide Phosphodiesterase 3B Is a Downstream Target of Protein Kinase B and May Be Involved in Regulation of Effects of Protein Kinase B on Thymidine Incorporation in FDCP2 Cells

Ahmad

Cong

Stenson

et al. 2000

The Journal of Immunology

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Wild-type (F/B), constitutively active (F/B*), and three kinase-inactive (F/Ba−, F/Bb−, F/Bc−) forms of Akt/protein kinase B (PKB) were permanently overexpressed in FDCP2 cells. In the absence of insulin-like growth factor-1 (IGF-1), activities of PKB, cyclic nucleotide phosphodiesterase 3B (PDE3B), and PDE4 were similar in nontransfected FDCP2 cells, mock-transfected (F/V) cells, and F/B and F/B− cells. In F/V cells, IGF-1 increased PKB, PDE3B, and PDE4 activities ∼2-fold. In F/B cells, IGF-1, in a wortmannin-sensitive manner, increased PKB activity ∼10-fold and PDE3B phosphorylation and activity (∼4-fold), but increased PDE4 to the same extent as in F/V cells. In F/B* cells, in the absence of IGF-1, PKB activity was markedly increased (∼10-fold) and PDE3B was phosphorylated and activated (3- to 4-fold); wortmannin inhibited these effects. In F/B* cells, IGF-1 had little further effect on PKB and activation/phosphorylation of PDE3B. In F/B− cells, IGF-1 activated PDE4, not PDE3B, suggesting that kinase-inactive PKB behaved as a dominant negative with respect to PDE3B activation. Thymidine incorporation was greater in F/B* cells than in F/V cells and was inhibited to a greater extent by PDE3 inhibitors than by rolipram, a PDE4 inhibitor. In F/B cells, IGF-1-induced phosphorylation of the apoptotic protein BAD was inhibited by the PDE3 inhibitor cilostamide. Activated PKB phosphorylated and activated rPDE3B in vitro. These results suggest that PDE3B, not PDE4, is a target of PKB and that activated PDE3B may regulate cAMP pools that modulate effects of PKB on thymidine incorporation and BAD phosphorylation in FDCP2 cells.

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“…Tumor necrosis factor (TNF)-␣ is one cytokine implicated in the exacerbation of asthma (3,6,10), and recent clinical studies raise hope that targeted therapy against TNF-␣ may improve asthma symptoms (6). Cyclic AMP is an important second messenger involved in the regulation of the contractile state, proliferation (8,25,34), migration (19), and cytokine secretory abilities (1) of airway smooth muscle cells. Previous studies in human airway smooth muscle cells have shown that cytokines, such as TNF-␣ and IL-1␤, directly influence cellular cAMP levels by "sensitizing" the activities of adenylyl cyclase enzymes (9,29), but the intracellular signaling pathways for the modification of adenylyl cyclase activity are unknown.…”

mentioning

confidence: 99%

Raf-1 kinase mediates adenylyl cyclase sensitization by TNF-α in human airway smooth muscle cells

Osawa¹,

Yim²,

Xu³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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Salbutamol inhibits the proliferation of human airway smooth muscle cells grown in culture: Relationship to elevated cAMP levels

Cited by 99 publications

References 39 publications

Phenotypic diversity and molecular mechanisms of airway smooth muscle proliferation in asthma

Phenotypic diversity and molecular mechanisms of airway smooth muscle proliferation in asthma

Cyclic Nucleotide Phosphodiesterase 3B Is a Downstream Target of Protein Kinase B and May Be Involved in Regulation of Effects of Protein Kinase B on Thymidine Incorporation in FDCP2 Cells

Raf-1 kinase mediates adenylyl cyclase sensitization by TNF-α in human airway smooth muscle cells

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