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Combined Beta-agonists and corticosteroids do not inhibit extracellular matrix protein production in vitro.

Ge Q, Poniris MH, Moir LM, Black JL, Burgess JK - J Allergy (Cairo) (2012)

Bottom Line: Whereas we have previously shown that neither β(2)-agonists nor corticosteroids inhibit extracellular matrix (ECM) protein release from airway smooth muscle (ASM) cells, the effect of their combination is unknown and this forms the rationale for the present study.Methods.Conclusion.

View Article: PubMed Central - PubMed

Affiliation: Division of Cell Biology, Woolcock Institute of Medical Research, Sydney, P.O. Box M77, Missenden Road, NSW 2050, Australia.

ABSTRACT
Background. Persistent asthma is characterized by airway remodeling. Whereas we have previously shown that neither β(2)-agonists nor corticosteroids inhibit extracellular matrix (ECM) protein release from airway smooth muscle (ASM) cells, the effect of their combination is unknown and this forms the rationale for the present study. Methods. ASM cells from people with and without asthma were stimulated with TGFβ1 (1 ng/ml) with or without budesonide (10(-8) M) and formoterol (10(-10) and 10(-8) M), and fibronectin expression and IL-6 release were measured by ELISA. Bronchial rings from nonasthmatic individuals were incubated with TGFβ1 (1 ng/ml) with or without the drugs, and fibronectin expression was measured using immunohistochemistry. Results. Budesonide stimulated fibronectin deposition, in the presence or absence of TGFβ1, and this was partially reversed by formoterol (10(-8) M) in both asthmatic and nonasthmatic cells. Budesonide and formoterol in combination failed to inhibit TGFβ-induced fibronectin in either cell type. A similar pattern of expression of fibronectin was seen in bronchial rings. TGFβ1-induced IL-6 release was inhibited by the combination of drugs. Conclusion. Current combination asthma therapies are unable to prevent or reverse remodeling events regulated by ASM cells.

No MeSH data available.


Related in: MedlinePlus

Effect of combined corticosteroids and LABAs on the release of IL-6 in the absence (a) or presence of TGFβ (b) for 48 hrs respectively. Data are mean ± SEM from n = 6 asthmatic (grey boxes) and n = 8 nonasthmatic (white boxes) ASM cell lines. Significantly different from nondrug-treated control *P < 0.05, #P < 0.005, $P < 0.001. F: formoterol, B: budesonide.
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fig2: Effect of combined corticosteroids and LABAs on the release of IL-6 in the absence (a) or presence of TGFβ (b) for 48 hrs respectively. Data are mean ± SEM from n = 6 asthmatic (grey boxes) and n = 8 nonasthmatic (white boxes) ASM cell lines. Significantly different from nondrug-treated control *P < 0.05, #P < 0.005, $P < 0.001. F: formoterol, B: budesonide.

Mentions: In nonasthmatic ASM cells, budesonide (10−8 M) alone significantly reduced the release of IL-6. The addition of formoterol (10−10 or 10−8 M) did not reverse this reduction (Figure 2(a) and Table 3). The release of IL-6 from asthmatic ASM cells was more variable but followed the same pattern.


Combined Beta-agonists and corticosteroids do not inhibit extracellular matrix protein production in vitro.

Ge Q, Poniris MH, Moir LM, Black JL, Burgess JK - J Allergy (Cairo) (2012)

Effect of combined corticosteroids and LABAs on the release of IL-6 in the absence (a) or presence of TGFβ (b) for 48 hrs respectively. Data are mean ± SEM from n = 6 asthmatic (grey boxes) and n = 8 nonasthmatic (white boxes) ASM cell lines. Significantly different from nondrug-treated control *P < 0.05, #P < 0.005, $P < 0.001. F: formoterol, B: budesonide.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3303634&req=5

fig2: Effect of combined corticosteroids and LABAs on the release of IL-6 in the absence (a) or presence of TGFβ (b) for 48 hrs respectively. Data are mean ± SEM from n = 6 asthmatic (grey boxes) and n = 8 nonasthmatic (white boxes) ASM cell lines. Significantly different from nondrug-treated control *P < 0.05, #P < 0.005, $P < 0.001. F: formoterol, B: budesonide.
Mentions: In nonasthmatic ASM cells, budesonide (10−8 M) alone significantly reduced the release of IL-6. The addition of formoterol (10−10 or 10−8 M) did not reverse this reduction (Figure 2(a) and Table 3). The release of IL-6 from asthmatic ASM cells was more variable but followed the same pattern.

Bottom Line: Whereas we have previously shown that neither β(2)-agonists nor corticosteroids inhibit extracellular matrix (ECM) protein release from airway smooth muscle (ASM) cells, the effect of their combination is unknown and this forms the rationale for the present study.Methods.Conclusion.

View Article: PubMed Central - PubMed

Affiliation: Division of Cell Biology, Woolcock Institute of Medical Research, Sydney, P.O. Box M77, Missenden Road, NSW 2050, Australia.

ABSTRACT
Background. Persistent asthma is characterized by airway remodeling. Whereas we have previously shown that neither β(2)-agonists nor corticosteroids inhibit extracellular matrix (ECM) protein release from airway smooth muscle (ASM) cells, the effect of their combination is unknown and this forms the rationale for the present study. Methods. ASM cells from people with and without asthma were stimulated with TGFβ1 (1 ng/ml) with or without budesonide (10(-8) M) and formoterol (10(-10) and 10(-8) M), and fibronectin expression and IL-6 release were measured by ELISA. Bronchial rings from nonasthmatic individuals were incubated with TGFβ1 (1 ng/ml) with or without the drugs, and fibronectin expression was measured using immunohistochemistry. Results. Budesonide stimulated fibronectin deposition, in the presence or absence of TGFβ1, and this was partially reversed by formoterol (10(-8) M) in both asthmatic and nonasthmatic cells. Budesonide and formoterol in combination failed to inhibit TGFβ-induced fibronectin in either cell type. A similar pattern of expression of fibronectin was seen in bronchial rings. TGFβ1-induced IL-6 release was inhibited by the combination of drugs. Conclusion. Current combination asthma therapies are unable to prevent or reverse remodeling events regulated by ASM cells.

No MeSH data available.


Related in: MedlinePlus