PMID- 16923814
OWN - NLM
STAT- MEDLINE
DCOM- 20061206
LR  - 20210219
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 281
IP  - 42
DP  - 2006 Oct 20
TI  - Ca2+- and protein kinase C-dependent signaling pathway for nuclear factor-kappaB 
      activation, inducible nitric-oxide synthase expression, and tumor necrosis 
      factor-alpha production in lipopolysaccharide-stimulated rat peritoneal 
      macrophages.
PG  - 31337-47
AB  - Lipopolysaccharide (LPS)-activated macrophages are pivotal in innate immunity. 
      With LPS treatment, extracellular signals are transduced into macrophages via 
      Toll-like receptor 4 and induce inflammatory mediator production by activating 
      signaling pathways, including the nuclear factor-kappaB (NF-kappaB) pathway and 
      the mitogen-activated protein kinase (MAPK) pathway. However, the mechanisms by 
      which the intracellular free Ca2+ concentration ([Ca2+]i) increases and protein 
      kinase C (PKC) is activated remain unclear. Therefore, we investigated the 
      signaling pathway for Ca2+- and PKC-dependent NF-kappaB activation, inducible 
      nitric-oxide synthase expression, and tumor necrosis factor-alpha (TNF-alpha) 
      production in LPS-stimulated rat peritoneal macrophages. The results demonstrated 
      that the LPS-induced transient [Ca2+]i increase is due to Ca2+ release and 
      influx. Extracellular and intracellular Ca2+ chelators inhibited phosphorylation 
      of PKCalpha and PKCbeta. A PKCbeta-specific and a general PKC inhibitor blunted 
      phosphorylation of serine in mitogen-activated/extracellular signal-regulated 
      kinase kinase kinase (MEKK) 1. Moreover, a MEKK inhibitor reduced activation of 
      inhibitorykappaB kinase and NF-kappaB. Upstream of the [Ca2+]i increase, a 
      protein-tyrosine kinase inhibitor reduced phosphorylation of phospholipase C 
      (PLC) gamma. Furthermore, a PLC inhibitor eliminated the transient [Ca2+]i 
      increase and decreased the amount of activated PKC. Therefore, these results 
      revealed the following roles of Ca2+ and PKC in the signaling pathway for 
      NF-kappaB activation in LPS-stimulated macrophages. After LPS treatment, 
      protein-tyrosine kinase mediates PLCgamma1/2 phosphorylation, which is followed 
      by a [Ca2+]i increase. Several PKCs are activated, and PKCbeta regulates 
      phosphorylation of serine in MEKK1. Moreover, MEKKs regulate inhibitory kappaB 
      kinase activation. Sequentially, NF-kappaB is activated, and inducible 
      nitric-oxide synthase and tumor necrosis factor-alpha production is promoted.
FAU - Zhou, Xueyuan
AU  - Zhou X
AD  - Department of Biophysics in the School of Physics, Key Laboratory of Bioactive 
      Materials of Education Ministry, Nankai University, Tianjin 300071, Peoples 
      Republic of China.
FAU - Yang, Wenxiu
AU  - Yang W
FAU - Li, Junying
AU  - Li J
LA  - eng
PT  - Journal Article
DEP - 20060821
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcium/*metabolism
MH  - *Gene Expression Regulation, Enzymologic
MH  - Lipopolysaccharides/*metabolism
MH  - Macrophages/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C3H
MH  - NF-kappa B/*metabolism
MH  - Nitric Oxide Synthase Type II/*biosynthesis
MH  - Peritoneum/*metabolism
MH  - Protein Kinase C/metabolism/*physiology
MH  - Rats
MH  - Rats, Wistar
MH  - *Signal Transduction
MH  - Tumor Necrosis Factor-alpha/*metabolism
EDAT- 2006/08/23 09:00
MHDA- 2006/12/09 09:00
CRDT- 2006/08/23 09:00
PHST- 2006/08/23 09:00 [pubmed]
PHST- 2006/12/09 09:00 [medline]
PHST- 2006/08/23 09:00 [entrez]
AID - S0021-9258(19)84046-2 [pii]
AID - 10.1074/jbc.M602739200 [doi]
PST - ppublish
SO  - J Biol Chem. 2006 Oct 20;281(42):31337-47. doi: 10.1074/jbc.M602739200. Epub 2006 
      Aug 21.