[Influence of atorvastatin on the expression of monocyte chemoattractant protein-1 in peritoneal mesothelial cells by high glucose].
OBJECTIVE
To investigate the influence of atorvastatin (ATOR) on the expression of monocyte chemoattractant protein-1 (MCP-1) induced by high concentration glucose in peritoneal mesothelial cells (PMCs) and the possible mechanism thereof.


METHODS
Rt PMCs were isolated, cultured, passaged, and divided into 3 groups: (1) treated with glucose of the concentrations of 0.1, 1.5, 2.5, 4.25% respectively, (2) treated with 1.5% glucose for 0, 0.5, 1, 3, 12, 24, and 48 h respectively, (3) pretreated with ammonium pyrrolidinedithiocarbomate (PDTC) of the concentrations of 5, 10, 25, or 50 micromol/L for 2 h, and then treated with 1.5% glucose for 3 h; and (4) pretreated with ATOR of the concentrations of 0.1, 1, or 10 mmol/L for 24 h, and then treated with 1.5% glucose for 3 h. Western blotting was used to measure the expression of MCP-1, p65, and inhibitor of nuclear factor-kappaBalpha (IkappaBalpha). RT-PCR was used to measure the expression of MCP-1 mRNA.


RESULTS
PMCs expressed MCP-1 in the normal condition. Glucose dose- and time-dependently reduced the protein expression of IkappaBalpha in the PMCs and increased the p65 expression in the nucleus, and accelerated the PMCs to express MCP-1 mRNA and protein (P < 0.05 and P < 0.01). PDTC dose-dependently inhibited the acceleration of expression of MCP-1 mRNA and protein in the PMCs induced by high concentration glucose (P < 0.05 or P < 0.01). ATOR dose-dependently increased the IkappaBalpha expression, decreased the p65 expression in nucleus, and decreased the expression of MCP-1 mRNA and protein (P < 0.05 or P < 0.01).


CONCLUSIONS
High concentration glucose induces PMCs to express MCP-1 in a time- and dose-dependent manner. Nuclear factor- kappaB (NF-kappaB) takes part in this regulation. ATOR inhibits PMCs to express MCP-1 through inhibiting NF-kappaB pathway.
Li
Zhi-ming
ZM
Department of Nephrology, First Affiliated Hospital of China Medical University, Shenyang 110001, China.
Ma
Jian-fei
JF
Wang
Li-ning
LN
D000818:Animals; D000069059:Atorvastatin; D015153:Blotting, Western; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D006538:Heptanoic Acids / Q000494:pharmacology*; D020672:I-kappa B Proteins / Q000096:biosynthesis; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D010537:Peritoneum / Q000166:cytology; D011758:Pyrroles / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D051996:Transcription Factor RelA / Q000096:biosynthesis
D018932:Chemokine CCL2; D006538:Heptanoic Acids; D020672:I-kappa B Proteins; C000606206:Nfkbia protein, rat; D011758:Pyrroles; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; D000069059:Atorvastatin; D005947:Glucose