Human lung and monocyte-derived macrophages differ with regard to the effects of β2-adrenoceptor agonists on cytokine releaseReportar como inadecuado




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Respiratory Research

, 18:126

First Online: 21 June 2017Received: 12 January 2017Accepted: 15 June 2017DOI: 10.1186-s12931-017-0613-y

Cite this article as: Victoni, T., Salvator, H., Abrial, C. et al. Respir Res 2017 18: 126. doi:10.1186-s12931-017-0613-y

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.

Keywordsβ2-adrenoceptor Cytokines Lipopolysaccharide Lung macrophage Monocyte-derived macrophage AbbreviationsBSABovine serum albumin

cAMPCyclic AMP

COPDChronic obstructive pulmonary disease

DMSODimethyl sulfoxide

FCSFetal calf serum

GAPDHGlyceraldehyde-3-phosphate dehydrogenase

HDMsHouse dust mites

ILInterleukin

LMsHuman lung macrophages

LPSLipopolysaccharide

LTB4Leukotriene B4

MDMsHuman monocyte-derived macrophages

PBSPhosphate-buffered saline

PDE4Phosphodiesterase 4

rhGM-CSFRecombinant human GM-CSF

TLR4Toll-like receptor 4

TNFTumor necrosis factor

TXB2Thromboxane B2

Electronic supplementary materialThe online version of this article doi:10.1186-s12931-017-0613-y contains supplementary material, which is available to authorized users.





Autor: Tatiana Victoni - Hélène Salvator - Charlotte Abrial - Marion Brollo - Luis Cristovão Sobrino Porto - Vincent Lagente -

Fuente: https://link.springer.com/







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