Inhibition of C-reactive protein induced expression of matrix metalloproteinases by atorvastatin in THP-1 cells.
The role of CRP as a mediator in atherosclerosis and inflammation is being investigated worldwide. In the present study, the effect of CRP on matrix metalloproteinases (MMP)-1, 2, 9, and their tissue inhibitor (TIMP-1) gene expression in THP-1 monocytic cell line was investigated. Specific mitogen activated protein (MAP) kinase (ERK, p38, and JNK) inhibitors were used to elucidate the signaling pathways involved. Effect of atorvastatin was determined in the presence of CRP on the expression of genes. Time and dose-dependent experiments were performed in the presence of CRP. The results showed that the treatment of THP-1 cells with 100 microg of CRP/ml/10(6) cells for 24 h enhanced the expression of MMPs and TIMP-1 genes significantly. CRP upregulated the expression of these genes via FcgammaRII and utilized ERK signaling pathway to transduce signals. Atorvastatin was able to significantly attenuate CRP-induced MMPs expression and augmented TIMP-1 gene expression significantly. In conclusion, CRP is not only a risk marker for vascular events, but also directly involved in the mechanisms leading to remodeling and destabilization of atherosclerotic plaque. Also, atorvastatin serves as potential therapeutic modality to curb these harmful events.
Mahajan
Nitin
N
Department of Experimental Medicine & Biotechnology, Postgraduate Institute of Medical Education & Research (PGIMER), Chandigarh, India.
Dhawan
Veena
V
D000924:Anticholesteremic Agents / Q000494:pharmacology; D000069059:Atorvastatin; D002097:C-Reactive Protein / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D011758:Pyrroles / Q000494:pharmacology*; D017452:Receptors, IgG / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism
D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D011758:Pyrroles; D017452:Receptors, IgG; D019715:Tissue Inhibitor of Metalloproteinase-1; D002097:C-Reactive Protein; D000069059:Atorvastatin; D020928:Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1