PKA-dependent activation of PKC, p38 MAPK and IKK in macrophage: implication in the induction of inducible nitric oxide synthase and interleukin-6 by dibutyryl cAMP

被引:100
作者
Chio, CC
Chang, YH
Hsu, YW
Chi, KH
Lin, WW [1 ]
机构
[1] Chi Mei Fdn Hosp, Dept Surg, Tainan, Taiwan
[2] Natl Taiwan Univ, Coll Med, Dept Pharmacol, Taipei 100, Taiwan
[3] Vet Gen Hosp, Ctr Canc, Taipei, Taiwan
关键词
dBcAMP; PKC; p38; MAPK; IKK; NF-kappa B; NO; IL-6; J774; macrophage;
D O I
10.1016/j.cellsig.2003.10.003
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
In this study, we examined the signal transduction of dibutyryl cyclic adenosine monophosphate (dBcAMP) to stimulate the release of nitric oxide (NO) and interleukin-6 (IL-6) from J774 macrophages. These actions of dBcAMP were diminished by the presence of the inhibitors of protein kinase A (PKA), protein kinase C (PKC), p38 MAPK and nuclear factor-kappa B (NF-kappaB). In contrast, Go 6976 and PD98059 had no significant effects. Consistently, dBcAMP caused membrane translocation of PKCbetaII, mu, lambda, zeta and isoforms, and increased atypical protein kinase C (aPKC) and p38 MAPK activities. The nuclear translocation and DNA-binding study revealed that dBcAMP stimulated NF-kappaB, activator protein-1 (AP-1), and CAAT/enhancer-binding protein (c/EBPbeta). Via PKA, PKC and p38 MAPK-dependent signals, dBcAMP also induced inhibitory subunit of NF-kappaB (IkappaB) degradation, IkappaB kinase (IKK) activation, nuclear translocation of NF-kappaB subunit p65 and its association with the CREB-binding protein (CBP). These results illustrate that PKA activation in macrophages is able to stimulate PKC and p38 MAPK, which lead to IKK-dependent NF-kappaB activation and contribute to the induction of inducible nitric oxide synthase (iNOS) and IL-6 genes. (C) 2003 Elsevier Inc. All rights reserved.
引用
收藏
页码:565 / 575
页数:11
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