Beta2-adrenoceptor agonist suppresses tumour necrosis factor production in rat mesangial cells.
This study aimed to investigate the time-course of the effect of beta2-adrenoceptor stimulation with terbutaline on lipopolysaccharide (LPS)-induced tumour necrosis factor(TNF)-alpha production in rat mesangial cells. Cells were cultured from 0-24 h in the presence of LPS (1 microg/ml) and/or terbutaline (10(-7)-10(-8) mol/l). After 1 h of incubation, terbutaline inhibited TNF-alpha protein release as well as transcription and translation of TNF-alpha and mitogen activated protein kinase (MAPK, p42/p44) activity. At 3 h, terbutaline enhanced intracellular cAMP but suppressed TNF-alpha release and transcription. By 24 h, whereas terbutaline was no longer influencing transcription or translation, TNF-alpha release remained depressed which correlated with an increase in supernatant interleukin (IL)-6. Terbutaline did not affect the LPS-induced IL-10 produced in the cell. These findings indicate that beta2-adrenoceptor stimulation during an LPS challenge prevented TNF-alpha production as a consequence of MAPK inhibition and enhanced cAMP generation, which at a later stage was associated with an anti-inflammatory effect of IL-6.
Nakamura
A
A
Department of Paediatrics, Teikyo University School of Medicine, Tokyo, Japan. akio@fuji.med.teikyo-u.ac.jp
Imaizumi
A
A
Kohsaka
T
T
Yanagawa
Y
Y
Johns
E J
EJ
D000318:Adrenergic beta-Agonists / Q000378:metabolism* / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008934:Mitogens / Q000276:immunology / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects; D051381:Rats; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D015398:Signal Transduction; D013726:Terbutaline / Q000378:metabolism* / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008934:Mitogens; D011412:Propanolamines; D018343:Receptors, Adrenergic, beta-2; D014409:Tumor Necrosis Factor-alpha; C026777:ICI 118551; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D013726:Terbutaline