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PDE4 inhibitors have no effect on eotaxin expression in human primary bronchial epithelial cells

100%

Paplinska-Goryca M., Chazan R., Grubek-Jaworska H.

Acta Biochimica Polonica

2012

tom 59

nr 3

The bronchial epithelium is a very important factor during the inflammatory response, it produces many key regulators involved in the pathophysiology of asthma and COPD. Local influx of eosinophils, basophils, Th2 lymphocytes and macrophages is the source of many cytotoxic proteins, cytokines and other mediators of inflammation. These cells are attracted by eotaxins (eotaxin-1/CCL11, eotaxin-2/CCL24, eotaxin-3/CCL26). Inhibitors of phosphodiesterase 4 (PDE4) are new anti-inflammatory drugs which cause cAMP accumulation in the cell and inhibit numerous stages of allergic inflammation. The aim of our study was to evaluate the influence of PDE4 inhibitors: rolipram and RO-20-1724 on the expression of eotaxins in human primary bronchial epithelial cells. Cells were preincubated with PDE4 inhibitors for 1 hour and then stimulated with IL-4 or IL-13 alone or in combination with TNF-α. After 48 hours, eotaxin protein level was measured by ELISA and mRNA level by real time PCR. These cells produce CCL24 and CCL26. PDE4 inhibitors increased CCL24 and CCL26 mRNA level irrespectively of the used stimulators. Rolipram and RO-20-1724 had no effect on eotaxin protein production in our experimental conditions. Thus PDE4 inhibitors have no effect on eotaxin protein expression in human primary bronchial epithelial cells. In vitro experiments should be performed using a primary cell model rather than immortalized lines.

The expression of the eotaxins IL-6 and CXCL8 in human epithelial cells from various levels of the respiratory tract

100%

Paplinska-Goryca M., Nejman-Gryz P., Chazan R., Grubek-Jaworska H.

Cellular and Molecular Biology Letters

2013

tom 18

nr 4

Airway epithelium acts as multifunctional site of response in the respiratory tract. Epithelial activity plays an important part in the pathophysiology of obstructive lung disease. In this study, we compare normal human epithelial cells from various levels of the respiratory tract in terms of their reactivity to pro-allergic and pro-inflammatory stimulation. Normal human nasal, bronchial and small airway epithelial cells were stimulated with IL-4 and IL-13. The expressions of the eotaxins IL-6 and CXCL8 were evaluated at the mRNA and protein levels. The effects of pre-treatment with IFN-γ on the cell reactivity were measured, and the responses to TNF-α, LPS and IFN-γ were evaluated. All of the studied primary cells expressed CCL26, IL-6 and IL-8 after IL-4 or IL-13 stimulation. IFN-γ pre-treatment resulted in decreased CCL26 and increased IL-6 expression in the nasal and small airway cells, but this effect was not observed in the bronchial cells. IL-6 and CXCL8 were produced in varying degrees by all of the epithelial primary cells in cultures stimulated with TNF-α, LPS or IFN-γ. We showed that epithelial cells from the various levels of the respiratory tract act in a united way, responding in a similar manner to stimulation with IL-4 and IL-13, showing similar reactivity to TNF-α and LPS, and giving an almost unified response to IFN-γ pre-stimulation.

Ograniczanie wyników

1 Acta Biochimica Polonica

1 Cellular and Molecular Biology Letters

2 Chazan R.

2 Grubek-Jaworska H.

2 Paplinska-Goryca M.

1 Nejman-Gryz P.

1 2013

1 2012

Wyniki wyszukiwania

PDE4 inhibitors have no effect on eotaxin expression in human primary bronchial epithelial cells

The expression of the eotaxins IL-6 and CXCL8 in human epithelial cells from various levels of the respiratory tract