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Cyclin D1 in ASM Cells from Asthmatics Is Insensitive to Corticosteroid Inhibition.

Allen JC, Seidel P, Schlosser T, Ramsay EE, Ge Q, Ammit AJ - J Allergy (Cairo) (2012)

Bottom Line: We examined the antiproliferative effectiveness of the corticosteroid dexamethasone on expression of the key regulator of G(1) cell cycle progression-cyclin D1-in ASM cells from nonasthmatics and asthmatics stimulated with the mitogen platelet-derived growth factor BB.This was independent of a repressive effect on glucocorticoid receptor translocation.Our results corroborate evidence demonstrating that corticosteroids inhibit mitogen-induced proliferation only in ASM cells from subjects without asthma and suggest that there are corticosteroid-insensitive proliferative pathways in asthmatics.

View Article: PubMed Central - PubMed

Affiliation: Respiratory Research Group, Faculty of Pharmacy, University of Sydney, Sydney, NSW 2006, Australia.

ABSTRACT
Hyperplasia of airway smooth muscle (ASM) is a feature of the remodelled airway in asthmatics. We examined the antiproliferative effectiveness of the corticosteroid dexamethasone on expression of the key regulator of G(1) cell cycle progression-cyclin D1-in ASM cells from nonasthmatics and asthmatics stimulated with the mitogen platelet-derived growth factor BB. While cyclin D1 mRNA and protein expression were repressed in cells from nonasthmatics in contrast, cyclin D1 expression in asthmatics was resistant to inhibition by dexamethasone. This was independent of a repressive effect on glucocorticoid receptor translocation. Our results corroborate evidence demonstrating that corticosteroids inhibit mitogen-induced proliferation only in ASM cells from subjects without asthma and suggest that there are corticosteroid-insensitive proliferative pathways in asthmatics.

No MeSH data available.


Related in: MedlinePlus

PDGF-BB upregulates cyclin D1 mRNA and protein expression in ASM from nonasthmatics and asthmatics. ASM cells from non-asthmatics and asthmatics were stimulated with 25 ng/mL of mitogen PDGF-BB. (a) demonstrates the temporal kinetics of cyclin D1 mRNA expression quantified by real-time RT-PCR (expressed as fold increase over 0 h). Statistical analysis was performed using one-way ANOVA, followed by Fisher's post hoc multiple comparison test (∗ denotes a significant effect of PDGF-BB on cyclin D1 mRNA, compared to 0 h (P < 0.05)). (b) shows densitometric analysis of cyclin D1 protein expression at 24 h quantified by western blotting (expressed as fold increase over 0 h), using α-tubulin as the loading control. Statistical analysis was performed using the Student's unpaired t-test (where ∗ denotes a significant effect of PDGF-BB on cyclin D1 protein, compared to 0 h (P < 0.05)). Values are mean + SE.
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fig1: PDGF-BB upregulates cyclin D1 mRNA and protein expression in ASM from nonasthmatics and asthmatics. ASM cells from non-asthmatics and asthmatics were stimulated with 25 ng/mL of mitogen PDGF-BB. (a) demonstrates the temporal kinetics of cyclin D1 mRNA expression quantified by real-time RT-PCR (expressed as fold increase over 0 h). Statistical analysis was performed using one-way ANOVA, followed by Fisher's post hoc multiple comparison test (∗ denotes a significant effect of PDGF-BB on cyclin D1 mRNA, compared to 0 h (P < 0.05)). (b) shows densitometric analysis of cyclin D1 protein expression at 24 h quantified by western blotting (expressed as fold increase over 0 h), using α-tubulin as the loading control. Statistical analysis was performed using the Student's unpaired t-test (where ∗ denotes a significant effect of PDGF-BB on cyclin D1 protein, compared to 0 h (P < 0.05)). Values are mean + SE.

Mentions: To examine the time course of induction of cyclin D1 mRNA by the mitogen PDGF-BB, growth-arrested ASM cells from non-asthmatic and asthmatic subjects were stimulated with PDGF-BB for up to 24 h. As shown in Figure 1(a), a significant increase in cyclin D1 mRNA expression was first detected 8 h after PDGF-BB treatment. By 24 h, cyclin D1 mRNA expression had further significantly increased to 2.6 ± 0.3-fold in ASM cells from non-asthmatics and 2.9 ± 0.3-fold in cells from asthmatics (P < 0.05). Interestingly, there was no significant difference between the increases in cyclin D1 upregulation in cells from asthmatics, as compared to nonasthmatic controls. Cyclin D1 protein expression at 24 h was similarly upregulated in support of the mRNA data Figure 1(b). Interestingly, there were no significant differences between the amount of cyclin D1 mRNA and protein expression in the asthmatics, as compared to non-asthmatics.


Cyclin D1 in ASM Cells from Asthmatics Is Insensitive to Corticosteroid Inhibition.

Allen JC, Seidel P, Schlosser T, Ramsay EE, Ge Q, Ammit AJ - J Allergy (Cairo) (2012)

PDGF-BB upregulates cyclin D1 mRNA and protein expression in ASM from nonasthmatics and asthmatics. ASM cells from non-asthmatics and asthmatics were stimulated with 25 ng/mL of mitogen PDGF-BB. (a) demonstrates the temporal kinetics of cyclin D1 mRNA expression quantified by real-time RT-PCR (expressed as fold increase over 0 h). Statistical analysis was performed using one-way ANOVA, followed by Fisher's post hoc multiple comparison test (∗ denotes a significant effect of PDGF-BB on cyclin D1 mRNA, compared to 0 h (P < 0.05)). (b) shows densitometric analysis of cyclin D1 protein expression at 24 h quantified by western blotting (expressed as fold increase over 0 h), using α-tubulin as the loading control. Statistical analysis was performed using the Student's unpaired t-test (where ∗ denotes a significant effect of PDGF-BB on cyclin D1 protein, compared to 0 h (P < 0.05)). Values are mean + SE.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3303636&req=5

fig1: PDGF-BB upregulates cyclin D1 mRNA and protein expression in ASM from nonasthmatics and asthmatics. ASM cells from non-asthmatics and asthmatics were stimulated with 25 ng/mL of mitogen PDGF-BB. (a) demonstrates the temporal kinetics of cyclin D1 mRNA expression quantified by real-time RT-PCR (expressed as fold increase over 0 h). Statistical analysis was performed using one-way ANOVA, followed by Fisher's post hoc multiple comparison test (∗ denotes a significant effect of PDGF-BB on cyclin D1 mRNA, compared to 0 h (P < 0.05)). (b) shows densitometric analysis of cyclin D1 protein expression at 24 h quantified by western blotting (expressed as fold increase over 0 h), using α-tubulin as the loading control. Statistical analysis was performed using the Student's unpaired t-test (where ∗ denotes a significant effect of PDGF-BB on cyclin D1 protein, compared to 0 h (P < 0.05)). Values are mean + SE.
Mentions: To examine the time course of induction of cyclin D1 mRNA by the mitogen PDGF-BB, growth-arrested ASM cells from non-asthmatic and asthmatic subjects were stimulated with PDGF-BB for up to 24 h. As shown in Figure 1(a), a significant increase in cyclin D1 mRNA expression was first detected 8 h after PDGF-BB treatment. By 24 h, cyclin D1 mRNA expression had further significantly increased to 2.6 ± 0.3-fold in ASM cells from non-asthmatics and 2.9 ± 0.3-fold in cells from asthmatics (P < 0.05). Interestingly, there was no significant difference between the increases in cyclin D1 upregulation in cells from asthmatics, as compared to nonasthmatic controls. Cyclin D1 protein expression at 24 h was similarly upregulated in support of the mRNA data Figure 1(b). Interestingly, there were no significant differences between the amount of cyclin D1 mRNA and protein expression in the asthmatics, as compared to non-asthmatics.

Bottom Line: We examined the antiproliferative effectiveness of the corticosteroid dexamethasone on expression of the key regulator of G(1) cell cycle progression-cyclin D1-in ASM cells from nonasthmatics and asthmatics stimulated with the mitogen platelet-derived growth factor BB.This was independent of a repressive effect on glucocorticoid receptor translocation.Our results corroborate evidence demonstrating that corticosteroids inhibit mitogen-induced proliferation only in ASM cells from subjects without asthma and suggest that there are corticosteroid-insensitive proliferative pathways in asthmatics.

View Article: PubMed Central - PubMed

Affiliation: Respiratory Research Group, Faculty of Pharmacy, University of Sydney, Sydney, NSW 2006, Australia.

ABSTRACT
Hyperplasia of airway smooth muscle (ASM) is a feature of the remodelled airway in asthmatics. We examined the antiproliferative effectiveness of the corticosteroid dexamethasone on expression of the key regulator of G(1) cell cycle progression-cyclin D1-in ASM cells from nonasthmatics and asthmatics stimulated with the mitogen platelet-derived growth factor BB. While cyclin D1 mRNA and protein expression were repressed in cells from nonasthmatics in contrast, cyclin D1 expression in asthmatics was resistant to inhibition by dexamethasone. This was independent of a repressive effect on glucocorticoid receptor translocation. Our results corroborate evidence demonstrating that corticosteroids inhibit mitogen-induced proliferation only in ASM cells from subjects without asthma and suggest that there are corticosteroid-insensitive proliferative pathways in asthmatics.

No MeSH data available.


Related in: MedlinePlus