title: L-cystathionine inhibits oxidized low density lipoprotein-induced THP-1-derived macrophage inflammatory cytokine monocyte chemoattractant protein-1 generation via the NF-κB pathway.
abstract: This study aimed to explore whether and how L-cystathionine had any regulatory effect on the inflammatory response in THP-1-derived macrophages cultured in vitro under oxidized low-density lipoprotein (ox-LDL) stimulation. The human monocyte line THP-1 cell was cultured in vitro and differentiated into macrophages after 24 hours of PMA induction. Macrophages were pretreated with L-cystathionine and then treated with ox-LDL. The results showed that compared with the controls, ox-LDL stimulation significantly upregulated the expression of THP-1-derived macrophage MCP-1 by enhancing NF-κB p65 phosphorylation, nuclear translocation and DNA binding with the MCP-1 promoter. Compared with the ox-LDL group, 0.3 mmol/L and 1.0 mmol/L L-cystathionine significantly inhibited the expression of THP-1-derived macrophage MCP-1. Mechanistically, 0.3 mmol/L and 1.0 mmol/L L-cystathionine suppressed phosphorylation and nuclear translocation of the NF-κB p65 protein, as well as the DNA binding activity and DNA binding level of NF-κB with the MCP-1 promoter, which resulted in a reduced THP-1-derived macrophage MCP-1 generation. This study suggests that L-cystathionine could inhibit the expression of MCP-1 in THP-1-derived macrophages induced by ox-LDL via inhibition of NF-κB p65 phosphorylation, nuclear translocation, and binding of the MCP-1 promoter sequence after entry into the nucleus.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, P. R. China.
authors.forename: Mingzhu
authors.initials: M
authors.lastname: Zhu
authors.affiliation: 1] Department of Pediatrics, Peking University First Hospital, Beijing 100034, P. R. China [2] Key Laboratory of Molecular Cardiology, Ministry of Education, Beijing 100191, P. R. China [3] Center for Molecular and Translational Medicine, Peking University Health Science Centre, Beijing 100191, P. R. China.
authors.forename: Junbao
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Medical and Health Sciences, Linköping University, Linköping 58183, Sweden.
authors.forename: Angie Dong
authors.initials: AD
authors.lastname: Liu
authors.affiliation: Department of Medical and Health Sciences, Linköping University, Linköping 58183, Sweden.
authors.forename: Lukas
authors.initials: L
authors.lastname: Holmberg
authors.affiliation: University of California, San Diego, La Jolla, California, 92093, United States of America.
authors.forename: Selena Y
authors.initials: SY
authors.lastname: Chen
authors.affiliation: Central Laboratory, Peking University First Hospital, Beijing 100034, P. R. China.
authors.forename: Dingfang
authors.initials: D
authors.lastname: Bu
authors.affiliation: 1] Key Laboratory of Molecular Cardiology, Ministry of Education, Beijing 100191, P. R. China [2] Department of Physiology and Pathophysiology, Peking University Health Science Centre, Beijing 100191, P. R. China.
authors.forename: Chaoshu
authors.initials: C
authors.lastname: Tang
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, P. R. China.
authors.forename: Hongfang
authors.initials: H
authors.lastname: Jin
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D003540:Cystathionine / Q000008:administration & dosage; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008077:Lipoproteins, LDL / Q000008:administration & dosage / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000235:genetics* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051996:Transcription Factor RelA / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D008077:Lipoproteins, LDL; D019402:Macrophage Inflammatory Proteins; D051996:Transcription Factor RelA; C099252:oxidized low density lipoprotein; D003540:Cystathionine