Interleukin-17-induced expression of monocyte chemoattractant protein-1 in cardiac myocytes requires nuclear factor κB through the phosphorylation of p65.

Abstract

IL-17 plays a key role in a variety of autoimmune diseases. MCP-1 is involved in the infiltration of mononuclear cells of myocardium in VMC. However, the relationship between IL-17 and MCP-1 in myocardial injury remains unclear. In this study, expression of MCP-1 mRNA and protein in cardiac myocytes was detected with qRT-PCR and ELISA, respectively. It was found that IL-17A induced MCP-1 expression in a dose- and time-dependent manner in cardiac myocytes, which could be blocked by IL-17A and IL-17RA neutralizing antibodies. NF-κB p65 and p-p65 protein expression in cardiac myocytes was studied with western blotting. Rates of p-p65 in whole lysates and in nuclear lysates all increased in the first 15 min. Meanwhile, the amount of NF-κB p65 in whole lysates did not change, but the amount of NF-κB p65 in nuclear lysates increased in the first 15 min. Then the optimal sequence and concentration of NF-κB p65 siRNAs was selected. After transfection of 10 nM siRNA-2 of NF-κB p65 into cardiac myocytes before stimulation by IL-17A, expression of MCP-1 mRNA and protein obviously decreased. In conclusion, expression of MCP-1 induced by IL-17 requires NF-κB through the phosphorylation of p65 in cardiac myocytes, which is meaningful to study the onset of chronic viral myocarditis and will provide a new target for the treatment of viral myocarditis.

• Authors: Yan Shen, Xin Xie, Zhuolun Li, Yan Huang, Li Ma, Xinhe Shen, Yanyue Liu, Yuxia Zhao
• Journal: Microbiology and immunology (Microbiol Immunol) Vol. 61 Issue 7 Pg. 280-286 (Jul 2017) ISSN: 1348-0421 [Electronic] Australia
• PMID: 28593659 (Publication Type: Journal Article)
• Copyright: © 2017 The Societies and John Wiley & Sons Australia, Ltd.

Chemical References

• Antibodies, Neutralizing
• Ccl2 protein, mouse
• Chemokine CCL2
• Interleukin-17
• NF-kappa B
• RNA, Messenger
• RNA, Small Interfering
• Recombinant Proteins
• Rela protein, mouse
• Transcription Factor RelA

Topics

• Animals
• Antibodies, Neutralizing (immunology, pharmacology)
• Cells, Cultured
• Chemokine CCL2 (antagonists & inhibitors, biosynthesis, immunology, metabolism)
• Dose-Response Relationship, Drug
• Interleukin-17 (immunology, metabolism, pharmacology)
• Mice
• Mice, Inbred BALB C
• Myocytes, Cardiac (drug effects, metabolism)
• NF-kappa B (metabolism)
• Phosphorylation
• RNA, Messenger (genetics, metabolism)
• RNA, Small Interfering (administration & dosage, metabolism)
• Recombinant Proteins (pharmacology)
• Transcription Factor RelA (metabolism)