beta(2)-Adrenoceptor agonist suppresses tumour necrosis factor production in rat mesangial cells

This study aimed to investigate the time-course of the effect of beta(2)-ad renoceptor 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 mu g/ml) and/or terbut aline (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 3h, terbutaline enhanced intracellular cAMP but suppressed TNF-alpha release a nd transcription. By 24 h, whereas terbutaline was no longer influencing tr anscription or translation, TNF-alpha release remained depressed which corr elated with an increase in supernatant interleukin (IL)-6, Terbutaline did not affect the LPS-induced IL-10 produced in the cell. These findings indic ate that beta(2)-adrenoceptor stimulation during an LPS challenge prevented TNF-alpha production as consequence of MAPK inhibition and enhanced cAMP g eneration, which at a later stage was associated with an anti-inflammatory effect of IL-6. (C) 2000 Academic Press.