PMID- 11820362
OWN - NLM
STAT- MEDLINE
DCOM- 20020215
LR  - 20190416
IS  - 0022-0345 (Print)
IS  - 0022-0345 (Linking)
VI  - 81
IP  - 1
DP  - 2002 Jan
TI  - Regulation of TNF-alpha-induced IL-6 production in MG-63 human osteoblast-like 
      cells.
PG  - 17-22
AB  - Tumor necrosis factor-alpha (TNF-alpha) stimulates osteoblast production of 
      interleukin-6 (IL-6), an inflammatory cytokine implicated in osteoclastic bone 
      resorption. Therefore, we tested the hypothesis that TNF-alpha-induced IL-6 
      production in MG-63 osteosarcoma cells occurs via the p38 mitogen-activated 
      protein kinase (MAPK) pathway. TNF-alpha activated p38 MAPK and stimulated IL-6 
      secretion by MG-63 cells, and pre-incubation of cells with the p38 MAPK inhibitor 
      abrogated TNF-alpha-dependent IL-6 secretion. Transfection of IL-6 full-length 
      and 5-deletion gene promoter reporter constructs indicated that p38 MAPK 
      activation by TNF-alpha enhanced IL-6 gene expression, and that the p38 
      MAPK-responsive region resided in the proximal 260-bp segment. Transfection of 
      NFkappaB and C/EBPbeta-sensitive reporter promoter constructs demonstrated that 
      NFkappaB activity was enhanced and that constitutive C/EBPbeta was inhibited by 
      TNF-alpha, with both effects being p38 MAPK-dependent. In conclusion, although 
      p38 MAPK activation by TNF-alpha stimulates IL-6 secretion by MG-63 cells, it has 
      opposing effects on c/EBPbeta and NFkappaB activity.
FAU - Webb, S J
AU  - Webb SJ
AD  - Dept. of Oral Biology, UNMC, Lincoln, NE 68583, USA.
FAU - McPherson, J R
AU  - McPherson JR
FAU - Pahan, K
AU  - Pahan K
FAU - Koka, S
AU  - Koka S
LA  - eng
GR  - DE12807/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Dent Res
JT  - Journal of dental research
JID - 0354343
RN  - 0 (CCAAT-Enhancer-Binding Protein-beta)
RN  - 0 (Interleukin-6)
RN  - 0 (NF-kappa B)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Analysis of Variance
MH  - CCAAT-Enhancer-Binding Protein-beta/physiology
MH  - Enzyme Activation
MH  - Gene Expression Regulation
MH  - Humans
MH  - Interleukin-6/*biosynthesis/genetics
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - NF-kappa B/physiology
MH  - Osteoblasts/*drug effects/enzymology/*metabolism
MH  - Osteosarcoma
MH  - Promoter Regions, Genetic
MH  - Statistics, Nonparametric
MH  - Transfection
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/*pharmacology/physiology
MH  - p38 Mitogen-Activated Protein Kinases
EDAT- 2002/02/01 10:00
MHDA- 2002/02/16 10:01
CRDT- 2002/02/01 10:00
PHST- 2002/02/01 10:00 [pubmed]
PHST- 2002/02/16 10:01 [medline]
PHST- 2002/02/01 10:00 [entrez]
AID - 10.1177/002203450208100105 [doi]
PST - ppublish
SO  - J Dent Res. 2002 Jan;81(1):17-22. doi: 10.1177/002203450208100105.