Participation of β-adrenergic receptors on macrophages in modulation of LPS-induced cytokine release
article
For several years it is known that β-adrenergic receptor agonists have anti-inflammatory effects. However, little is known about the role of β- adrenergic receptors on macrophages in the modulation of cytokine production by β-agonists during inflammation. In this study, the presence of β- receptors on PMA-differentiated U937 human macrophages, and the participation of these receptors in the modulation of LPS-mediated cytokine production by β-agonists was investigated. Total β-receptor expression on undifferentiated (monocyte) and PMA-differentiated U937 cells was established using receptor binding studies on membrane fractions with a radio ligand. The expression of β-receptors proved to be significantly lower on monocytes than on macrophages, additionally a predominant expression of β2-receptors was found. Production of the cytokines TNF-α, IL-6, and IL-10 by LPS-stimulated differentiated U937 cells was measured in time. Peak concentrations for TNF- α, IL-76 and IL-10 occurred at 3, 12 and 9 hrs, respectively. When differentiated U937 cells were incubated with both LPS and the β-agonist clenbuterol the production of TNF-α and IL-6 was significantly reduced. However the production of IL-10 was increased. To study the mechanism of modulation of cytokine production in more detail, U937 macrophages were incubated with LPS/clenbuterol in combination with selective β1- and β2- antagonists. These results indicated that the β2- and not the β1- receptor is involved in the anti-inflammatory activity of clenbuterol.
Chemicals/CAS: Adrenergic beta-Agonists; Adrenergic beta-Antagonists; Atenolol, 29122-68-7; Clenbuterol, 37148-27-9; Cytokines; ICI 118551, 72795-19-8; Interleukin-10, 130068-27-8; Interleukin-6; Lipopolysaccharides; Propanolamines; Receptors, Adrenergic, beta; Tumor Necrosis Factor-alpha
Chemicals/CAS: Adrenergic beta-Agonists; Adrenergic beta-Antagonists; Atenolol, 29122-68-7; Clenbuterol, 37148-27-9; Cytokines; ICI 118551, 72795-19-8; Interleukin-10, 130068-27-8; Interleukin-6; Lipopolysaccharides; Propanolamines; Receptors, Adrenergic, beta; Tumor Necrosis Factor-alpha
Topics
Beta 2 adrenergic receptor stimulating agentBeta adrenergic receptorClenbuterolCytokineInterleukin 10Interleukin 6LipopolysaccharideRadioligandTumor necrosis factor alphaAntiinflammatory activityCell cultureConference paperCytokine productionDrug receptor bindingHumanHuman cellInflammationMacrophageMacrophage activationMonocyteReceptor bindingReceptor intrinsic activityAdrenergic beta-AgonistsAdrenergic beta-AntagonistsAtenololClenbuterolCytokinesHumansInterleukin-10Interleukin-6LipopolysaccharidesMacrophage ActivationMacrophagesPropanolaminesReceptors, Adrenergic, betaTumor Necrosis Factor-alphaU937 Cells
TNO Identifier
235001
ISSN
10799893
Source
Journal of Receptor and Signal Transduction Research, 19(1-4), pp. 191-202.
Pages
191-202
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