PMID- 12716761
OWN - NLM
STAT- MEDLINE
DCOM- 20030711
LR  - 20240109
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 52
IP  - 5
DP  - 2003 May
TI  - High glucose-induced expression of proinflammatory cytokine and chemokine genes 
      in monocytic cells.
PG  - 1256-64
AB  - Monocyte activation and adhesion to the endothelium play important roles in 
      inflammatory and cardiovascular diseases. These processes are further aggravated 
      by hyperglycemia, leading to cardiovascular complications in diabetes. We have 
      previously shown that high glucose (HG) treatment activates monocytes and induces 
      the expression of tumor necrosis factor (TNF)-alpha via oxidant stress and 
      nuclear factor-kB transcription factor. To determine the effects of HG on the 
      expression of other inflammatory genes, in the present study, HG-induced gene 
      profiling was performed in THP-1 monocytes using cytokine gene arrays containing 
      375 known genes. HG treatment upregulated the expression of 41 genes and 
      downregulated 15 genes that included chemokines, cytokines, chemokines receptors, 
      adhesion molecules, and integrins. RT-PCR analysis further confirmed that HG 
      significantly increased the expression of monocyte chemoattractant protein-1 
      (MCP-1), TNF-alpha, beta(2)-integrin, interleukin-1beta, and others. HG treatment 
      increased transcription of the MCP-1 gene, MCP-1 protein levels, and adhesion of 
      THP-1 cells to endothelial cells. HG-induced MCP-1 mRNA expression and monocyte 
      adhesion were blocked by specific inhibitors of oxidant stress, protein kinase C, 
      ERK1/2, and p38 mitogen-activated protein kinases. These results show for the 
      first time that multiple inflammatory cytokines and chemokines relevant to the 
      pathogenesis of diabetes complications are induced by HG via key signaling 
      pathways.
FAU - Shanmugam, Narkunaraja
AU  - Shanmugam N
AD  - Department of Diabetes, Beckman Research Institute of City of Hope, 1500 East 
      Duarte Road, Duarte, CA 91010, USA.
FAU - Reddy, Marpadga A
AU  - Reddy MA
FAU - Guha, Mausumee
AU  - Guha M
FAU - Natarajan, Rama
AU  - Natarajan R
LA  - eng
GR  - R01 DK065073/DK/NIDDK NIH HHS/United States
GR  - P01 HL 55798/HL/NHLBI 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  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (DNA Primers)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Imidazoles)
RN  - 0 (Pyridines)
RN  - IY9XDZ35W2 (Glucose)
RN  - PVX798P8GI (4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/pharmacology
MH  - Base Sequence
MH  - Cell Line
MH  - Chemokines/classification/*genetics
MH  - Cytokines/classification/*genetics
MH  - DNA Primers
MH  - Enzyme Inhibitors/pharmacology
MH  - Gene Expression Regulation/drug effects/*immunology
MH  - Glucose/*pharmacology
MH  - Humans
MH  - Imidazoles/pharmacology
MH  - Monocytes/drug effects/*immunology
MH  - Oligonucleotide Array Sequence Analysis/methods
MH  - Polymerase Chain Reaction
MH  - Pyridines/pharmacology
EDAT- 2003/04/30 05:00
MHDA- 2003/07/12 05:00
CRDT- 2003/04/30 05:00
PHST- 2003/04/30 05:00 [pubmed]
PHST- 2003/07/12 05:00 [medline]
PHST- 2003/04/30 05:00 [entrez]
AID - 10.2337/diabetes.52.5.1256 [doi]
PST - ppublish
SO  - Diabetes. 2003 May;52(5):1256-64. doi: 10.2337/diabetes.52.5.1256.