Abstract
Backgroundβ2-adrenoceptor agonists have been shown to reduce the lipopolysaccharide (LPS)-induced cytokine release by human monocyte-derived macrophages (MDMs). We compare the expression of β2-adrenoceptors and the inhibitory effect of formoterol and salmeterol on the LPS-induced release of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and a range of chemokines (CCL2, 3, 4, and IL-8) by human lung macrophages (LMs) and MDMs.MethodsLMs were isolated from patients undergoing resection and MDMs were obtained from blood monocytes in the presence of GM-CSF. LMs and MDMs were incubated in the absence or presence of formoterol or salmeterol prior to stimulation with LPS. The effects of formoterol were also assessed in the presence of the phosphodiesterase inhibitor roflumilast.ResultsLPS-induced cytokine production was higher in LMs than in MDMs. Salmeterol and formoterol exerted an inhibitory effect on the LPS-induced production of TNF-α, IL-6, CCL2, CCL3, and CCL4 in MDMs. In contrast, the β2-adrenoceptor agonists were devoid of any effect on LMs - even in the presence of roflumilast. The expression of β2-adrenergic receptors was detected on Western blots in MDMs but not in LMs.ConclusionsConcentrations of β2-adrenoceptor agonists that cause relaxation of the human bronchus can inhibit cytokine production by LPS-stimulated MDMs but not by LMs.
Highlights
Pollens, house dust mites (HDMs), and cat dander are major triggers in allergic respiratory diseases such as asthma [1,2,3]
Effects of LPS on cytokine production by monocyte-derived macrophages (MDMs) and lung macrophages (LMs) There was no significant difference between unstimulated LMs and MDMs in terms of the production of tumor necrosis factor (TNF)-α, IL-1β, and the chemokines (IL-8, CCL2, CCL3, and CCL4)
Following incubation with LPS, the release of all cytokines other than TNF-α and CCL4 was greater for LMs than for MDMs (Table 1)
Summary
House dust mites (HDMs), and cat dander are major triggers in allergic respiratory diseases such as asthma [1,2,3]. (TLR4) is involved in the airways’ response to various allergens (e.g. ragweed pollen, house dust extract, and cat dander) and many air pollutants including particulate matter and their components other than allergens and LPS, such as viruses and fungal spores [6,7,8,9]. LPS-mediated activation of macrophages causes the release of cytokines (tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and chemokines such as CCL2, CCL3, CCL4, and CXCL8 (IL-8)). This release contributes to airway inflammation by increasing the recruitment of inflammatory cells [10].
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