Beta2-Agonist Induced Camp Is Decreased In Asthmatic Airway Smooth Muscle Due To Increased PDE4D

Trian, Thomas; Moir, Lyn M.; Burgess, Janette K.; Liggett, Stephen B.; Ge, Qi; Black, Judith L.; Oliver, Brian G.

doi:10.1164/ajrccm-conference.2011.183.1_meetingabstracts.a2075

Cited by 2 publications

(1 citation statement)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our study suggests that this reduction of neutrophils may be due to the ability of PDE 4 inhibitors to modulate IL-6 and also IL-8 levels in ASMCs and therefore limit neutrophil recruitment [ 38 ]. PDE 4 inhibitors have been shown to synergistically increase the effects of β 2 -AR agonists, and dual specific PDE 4/3 inhibitors have been shown to cause acute short acting bronchodilation in people with asthma [ 55 - 57 ]. We demonstrated for the first time that PDE 4 inhibitors do not alter RV replication or the inflammatory response to RV infections in ASMCs and HBECs.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of phosphodiesterase 4 modulates cytokine induction from toll like receptor activated, but not rhinovirus infected, primary human airway smooth muscle

Ly¹,

Pedro²,

James³

et al. 2013

Respir Res

View full text Add to dashboard Cite

BackgroundVirus-induced exacerbations of Chronic Obstructive Pulmonary Disease (COPD) are a significant health burden and occur even in those receiving the best current therapies. Rhinovirus (RV) infections are responsible for half of all COPD exacerbations. The mechanism by which exacerbations occur remains undefined, however it is likely to be due to virus-induced inflammation. Given that phophodiesterase 4 (PDE4) inhibitors have an anti-inflammatory effect in patients with COPD they present a potential therapy prior to, and during, these exacerbations.MethodsIn the present study we investigated whether the PDE4 inhibitor piclamilast (10-6 M) could alter RV or viral mimetic (5 μg/mL of imiquimod or poly I:C) induced inflammation and RV replication in primary human airway smooth muscle cells (ASMC) and bronchial epithelial cells (HBEC). The mediators IL-6, IL-8, prostaglandin E2 and cAMP production were assayed by ELISA and RV replication was assayed by viral titration.ResultsWe found that in ASMCs the TLR3 agonist poly I:C induced IL-8 release was reduced while induced IL-6 release by the TLR7/8 agonist imiquimod was further increased by the presence of piclamilast. However, in RV infected ASMCs, virus replication and induced mediator release were unaltered by piclamilast, as was also found in HBECs. The novel findings of this study reveal that although PDE inhibitors may not influence RV-induced cytokine production in ASMCs and replication in either ASMCs or HBECs, they have the capacity to be anti-inflammatory during TLR activation by modulating the induction of these chemotactic cytokines.ConclusionBy extrapolating our in vitro findings to exacerbations of COPD in vivo this suggests that PDE4 inhibitors may have beneficial anti-inflammatory properties when patients are infected with bacteria or viruses other than RV.

show abstract

Section: Discussionmentioning

confidence: 99%

Inhibition of phosphodiesterase 4 modulates cytokine induction from toll like receptor activated, but not rhinovirus infected, primary human airway smooth muscle

Ly¹,

Pedro²,

James³

et al. 2013

Respir Res

View full text Add to dashboard Cite

show abstract

Differential effects of extracellular matrix and mechanical strain on airway smooth muscle cells from ovalbumin- vs saline-challenged Brown Norway rats

Pasternyk

D’Antoni

Venkatesan

et al. 2012

Respiratory Physiology & Neurobiology

View full text Add to dashboard Cite

Beta2-Agonist Induced Camp Is Decreased In Asthmatic Airway Smooth Muscle Due To Increased PDE4D

Abstract: Background and Objective: Asthma is associated with airway narrowing in response to bronchoconstricting stimuli and increased airway smooth muscle (ASM) mass. In addition, some studies have suggested impaired b-agonist induced ASM relaxation in asthmatics, but the mechanism is not known.

Cited by 2 publications

References 25 publications

Inhibition of phosphodiesterase 4 modulates cytokine induction from toll like receptor activated, but not rhinovirus infected, primary human airway smooth muscle

Inhibition of phosphodiesterase 4 modulates cytokine induction from toll like receptor activated, but not rhinovirus infected, primary human airway smooth muscle

Differential effects of extracellular matrix and mechanical strain on airway smooth muscle cells from ovalbumin- vs saline-challenged Brown Norway rats

Contact Info

Product

Resources

About