PMID- 18003754
OWN - NLM
STAT- MEDLINE
DCOM- 20080425
LR  - 20211020
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 57
IP  - 4
DP  - 2008 Apr
TI  - Proinflammatory effects of advanced lipoxidation end products in monocytes.
PG  - 879-88
AB  - OBJECTIVE: The reactions of carbohydrate- or lipid-derived intermediates with 
      proteins lead to the formation of Maillard reaction products, which subsequently 
      leads to the formation of advanced glycation/lipoxidation end products 
      (AGE/ALEs). Levels of AGE/ALEs are increased in diseases like diabetes. Unlike 
      AGEs, very little is known about ALE effects in vitro. We hypothesized that ALEs 
      can have proinflammatory effects in monocytes. RESEARCH DESIGN AND METHODS: In a 
      profiling approach, conditioned media from THP-1 cells either cultured in normal 
      glucose (5.5 mmol/l) or treated with MDA-Lys or MDA alone were hybridized to 
      arrays containing antibodies to 120 known human cytokines/chemokines. Pathway 
      analyses with bioinformatics software were used to identify signalling networks. 
      RESULTS: Synthetic ALE (malondialdehyde-lysine [MDA-Lys]) (50 micromol/l) could 
      induce oxidant stress and also activate the transcriptional factor nuclear 
      factor-kappaB (NF-kappaB) in THP-1 monocytes. MDA-Lys also significantly 
      increased the expression of key candidate proinflammatory genes, 
      interferon-gamma-inducible protein-10, beta1- and beta2-integrins, 
      cyclooxygenase-2 (COX-2), monocyte chemoattractant protein-1 (MCP-1), 
      interleukin-6 and -8, and inducible nitric-oxide synthase, which are also 
      associated with monocyte dysfunction. Several key target proinflammatory proteins 
      were significantly induced by MDA-Lys relative to normal glucose or MDA alone, 
      including MCP-1; tumor necrosis factor ligand superfamily member-14; chemokine CC 
      motif ligand-11 (CCL11); growth-related oncogene-alpha, -beta, and -gamma; and 
      chemokine CXC motif ligand-13. Bioinformatics analyses identified a network of 
      chemokine signaling among MDA-Lys-regulated genes. MDA-Lys also increased 
      monocyte binding to vascular smooth muscle and endothelial cells. Furthermore, 
      plasma from diabetic rats showed significantly higher levels of MDA-Lys and 
      CCL11. CONCLUSIONS: These new results suggest that ALEs can promote monocyte 
      activation and vascular complications via induction of inflammatory pathways and 
      networks.
FAU - Shanmugam, Narkunarajaa
AU  - Shanmugam N
AD  - Department of Diabetes, Beckman Research Institute of the City of Hope, 1500 East 
      Duarte Rd., Duarte, CA 91010, USA.
FAU - Figarola, James L
AU  - Figarola JL
FAU - Li, Yan
AU  - Li Y
FAU - Swiderski, Piotr M
AU  - Swiderski PM
FAU - Rahbar, Samual
AU  - Rahbar S
FAU - Natarajan, Rama
AU  - Natarajan R
LA  - eng
GR  - M01 RR000043/RR/NCRR NIH HHS/United States
GR  - R01 DK065073/DK/NIDDK NIH HHS/United States
GR  - R01 DK065073-06/DK/NIDDK NIH HHS/United States
GR  - MO1RR00043/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20071114
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Glycation End Products, Advanced)
RN  - 0 (N(epsilon)-(malondialdehyde)lysine)
RN  - 0 (NF-kappa B)
RN  - 0 (Receptors, CCR2)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - IY9XDZ35W2 (Glucose)
RN  - K3Z4F929H6 (Lysine)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/pharmacology
MH  - Animals
MH  - Cell Line
MH  - Cyclooxygenase 2/genetics
MH  - Gene Expression Regulation, Enzymologic/drug effects
MH  - Glucose/pharmacology
MH  - Glycation End Products, Advanced/*metabolism
MH  - Humans
MH  - Inflammation/*physiopathology
MH  - Lipid Peroxidation/*physiology
MH  - Lysine/analogs & derivatives/blood/pharmacology
MH  - Monocytes/*cytology/drug effects/*physiology
MH  - NF-kappa B/drug effects/*metabolism
MH  - Rats
MH  - Receptors, CCR2/genetics
PMC - PMC2695452
MID - NIHMS103865
EDAT- 2007/11/16 09:00
MHDA- 2008/04/26 09:00
PMCR- 2009/06/11
CRDT- 2007/11/16 09:00
PHST- 2007/11/16 09:00 [pubmed]
PHST- 2008/04/26 09:00 [medline]
PHST- 2007/11/16 09:00 [entrez]
PHST- 2009/06/11 00:00 [pmc-release]
AID - db07-1204 [pii]
AID - 10.2337/db07-1204 [doi]
PST - ppublish
SO  - Diabetes. 2008 Apr;57(4):879-88. doi: 10.2337/db07-1204. Epub 2007 Nov 14.