Activation of cannabinoid CB2 receptor negatively regulates IL-12p40 production in murine macrophages: role of IL-10 and ERK1/2 kinase signaling.

来自 EBSCO

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摘要：

1 Cannabinoid (CB) receptor agonists have potential utility as anti-inflammatory drugs for the treatment of many disease conditions. In the present study, we investigated the effects of the synthetic CB 2 ligand, JWH-133 on the production of interleukins (ILs), IL-12 and IL-10 by lipopolyssacharide (LPS) or Theiler's virus (TMEV)-activated macrophages. 2 JWH-133 evoked a concentration-related inhibition (10 n M 5 M ) of LPS/IFN- induced IL-12p40 release. The effect of JWH-133 (100 n M ) was significantly blocked by the CB 2 antagonist SR-144528 (1 M ). Macrophages infected with TMEV increased IL-12p40 production and activation of CB 2 receptors by JWH-133 (100 n M ) inhibited it. 3 The inhibitory effect of JWH-133 (100 n M ) on IL-12p40 production may involve extracellular-regulated kinase (ERK1/2) signaling: (i) JWH-133 induced a greater and sustained activation of ERK1/2 kinase in comparison with the level of activation observed following LPS; (ii) the inhibition of ERK1/2 by the specific inhibitor PD98059 increased LPS-induced IL-12p40 production in the presence or absence of JWH-133 suggesting a negative regulation of ERK pathway on IL-12p40 biosynthesis. 4 Activation of CB 2 receptors by JWH-133 (10 n M 5 M ) enhanced IL-10 release by LPS/IFN- -activated macrophages and addition of SR144558 (1 M ) totally blocked the effect of JWH (100 n M ). 5 Inhibition of ERK by PD98059 significantly suppressed IL-10 production by LPS-activated macrophages. Endogenous IL-10 plays a modulatory role in IL-12 production. Blocking IL-10 with neutralizing antibody resulted in increased IL-12p40 secretion by LPS-activated macrophages in the absence or presence of JWH-133. In contrast, the addition of exogenous mIL-10 reduced the secretion of IL-12p40 in response to LPS. British Journal of Pharmacology (2005) 145 , 441448. doi: [DOI link]

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关键词：

Cannabinoids CB<SUB> 2 </SUB> receptors IL-12p40 IL-10 ERK1/2 macrophages

DOI：

10.1038/sj.bjp.0706215

被引量：

150

年份：

2005