PMID- 20082310
OWN - NLM
STAT- MEDLINE
DCOM- 20100506
LR  - 20191210
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Linking)
VI  - 223
IP  - 2
DP  - 2010 May
TI  - FAK activation is required for TNF-alpha-induced IL-6 production in myoblasts.
PG  - 389-96
LID - 10.1002/jcp.22047 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a pleiotropic cytokine produced by 
      activated macrophages. IL-6 is a multifunctional cytokine that plays a central 
      role in both innate and acquired immune responses. We investigated the signaling 
      pathway involved in IL-6 production stimulated by TNF-alpha in cultured 
      myoblasts. TNF-alpha caused concentration-dependent increases in IL-6 production. 
      TNF-alpha-mediated IL-6 production was attenuated by focal adhesion kinase (FAK) 
      mutant and siRNA. Pretreatment with phosphatidylinositol 3-kinase inhibitor 
      (PI3K; Ly294002 and wortmannin), Akt inhibitor, NF-kappaB inhibitor (pyrrolidine 
      dithiocarbamate, PDTC), and IkappaB protease inhibitor (L-1-tosylamido-2-phenyl 
      phenylethyl chloromethyl ketone, TPCK) also inhibited the potentiating action of 
      TNF-alpha. TNF-alpha increased the FAK, PI3K, and Akt phosphorylation. 
      Stimulation of myoblasts with TNF-alpha activated IkappaB kinase alpha/beta 
      (IKKalpha/beta), IkappaBalpha phosphorylation, p65 phosphorylation, and 
      kappaB-luciferase activity. TNF-alpha mediated an increase of kappaB-luciferase 
      activity which was inhibited by Ly294002, wortmannin, Akt inhibitor, PDTC and 
      TPCK or FAK, PI3K, and Akt mutant. Our results suggest that TNF-alpha increased 
      IL-6 production in myoblasts via the FAK/PI3K/Akt and NF-kappaB signaling 
      pathway.
FAU - Tseng, Wen-Pei
AU  - Tseng WP
AD  - Graduate Institute of Sports and Health, National Changhua University of 
      Education, Changhua County, Taiwan.
FAU - Su, Chen-Ming
AU  - Su CM
FAU - Tang, Chih-Hsin
AU  - Tang CH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Interleukin-6)
RN  - 0 (NF-kappa B)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.10.2 (Focal Adhesion Kinase 1)
RN  - EC 2.7.10.2 (Ptk2 protein, mouse)
RN  - EC 2.7.11.1 (Oncogene Protein v-akt)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Inhibitors/pharmacology
MH  - Focal Adhesion Kinase 1/genetics/*metabolism
MH  - Interleukin-6/*biosynthesis
MH  - Mice
MH  - Muscle Development/*physiology
MH  - Muscle, Skeletal/growth & development/*metabolism
MH  - Myoblasts/cytology/*metabolism
MH  - NF-kappa B/metabolism
MH  - Oncogene Protein v-akt/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Phosphorylation
MH  - RNA Interference
MH  - Signal Transduction/drug effects/physiology
MH  - Tumor Necrosis Factor-alpha/*metabolism/pharmacology
EDAT- 2010/01/19 06:00
MHDA- 2010/05/07 06:00
CRDT- 2010/01/19 06:00
PHST- 2010/01/19 06:00 [entrez]
PHST- 2010/01/19 06:00 [pubmed]
PHST- 2010/05/07 06:00 [medline]
AID - 10.1002/jcp.22047 [doi]
PST - ppublish
SO  - J Cell Physiol. 2010 May;223(2):389-96. doi: 10.1002/jcp.22047.