Nakamura A, Imaizumi A, Kohsaka T, Yanagawa Y, Johns E J
Department of Paediatrics, Teikyo University School of Medicine, Tokyo, Japan.
Cytokine. 2000 May;12(5):491-4. doi: 10.1006/cyto.1999.0581.
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.
本研究旨在探讨用特布他林刺激β2-肾上腺素能受体对脂多糖（LPS）诱导的大鼠系膜细胞肿瘤坏死因子（TNF）-α产生的时间效应过程。细胞在LPS（1微克/毫升）和/或特布他林（10^(-7)-10^(-8)摩尔/升）存在的情况下培养0至24小时。孵育1小时后，特布他林抑制TNF-α蛋白释放以及TNF-α的转录和翻译，并抑制丝裂原活化蛋白激酶（MAPK，p42/p44）活性。3小时时，特布他林增强细胞内cAMP，但抑制TNF-α释放和转录。到24小时时，虽然特布他林不再影响转录或翻译，但TNF-α释放仍受到抑制，这与上清液中白细胞介素（IL）-6增加相关。特布他林不影响细胞中LPS诱导产生的IL-10。这些发现表明，在LPS刺激期间，β2-肾上腺素能受体刺激通过抑制MAPK和增强cAMP生成来阻止TNF-α产生，而在后期这与IL-6的抗炎作用相关。
