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[Homocysteine induces macrophage inflammatory protein-1alpha expression by activating NF-kappaB in THP-1 monocytes]
Wei Xing1, Zhong-Duan Deng, Zhi-Ling Qu
1Department of Pathology, Tongji Medical College, Huazhong University of Science Technology, Wuhan 430030, China. grace_xingw@yahoo.com.cn
Zhonghua Bing Li Xue Za Zhi = Chinese Journal of Pathology
|April 22, 2005
Summary
Pathologic homocysteine (HCY) levels increase macrophage inflammatory protein (MIP-1alpha) in THP-1 cells by activating nuclear factor-kappaB (NF-kappaB). This inflammatory response is linked to IkappaB-alpha degradation.
Area of Science:
- Cellular and Molecular Biology
- Immunology
- Biochemistry
Background:
- Homocysteine (HCY) is an amino acid linked to cardiovascular disease.
- Nuclear factor-kappaB (NF-kappaB) is a key regulator of inflammatory responses.
- Macrophage inflammatory protein-1alpha (MIP-1alpha) is a pro-inflammatory cytokine.
Purpose of the Study:
- To investigate the effect of HCY on NF-kappaB activation and IkappaB-alpha in THP-1 monocytes.
- To determine the association between HCY, NF-kappaB, and MIP-1alpha upregulation.
Main Methods:
- THP-1 monocytes were treated with HCY, with and without the NF-kappaB inhibitor pyrolidine dithiocarbamate (PDTC).
- MIP-1alpha mRNA and protein levels were assessed using Northern blot and flow cytometry.
- NF-kappaB P65 and IkappaB-alpha protein levels were analyzed by Western blotting.
Main Results:
- HCY (0.1 mmol/L) significantly enhanced MIP-1alpha mRNA and protein expression in THP-1 cells.
- HCY increased NF-kappaB P65 transcription to nuclear proteins.
- PDTC pretreatment suppressed HCY-induced MIP-1alpha expression and NF-kappaB activation.
- HCY treatment led to a decrease in IkappaB-alpha protein levels.
Conclusions:
- Pathologic concentrations of HCY stimulate MIP-1alpha expression in monocytes, likely through NF-kappaB activation.
- HCY-induced NF-kappaB activation may involve enhanced phosphorylation and degradation of IkappaB-alpha.