Homocysteine at pathophysiologic concentrations activates human monocyte and induces cytokine expression and inhibits macrophage migration inhibitory factor expression.
OBJECTIVE
Homocystinemia is an important independent risk factor for atherosclerosis. Inflammatory cytokines play key roles in the development of atherogenesis. This study investigated the effect of homocysteine on inflammatory cytokine expression.


METHODS
Human monocytes were treated in vitro with a variety of DL-homocysteine concentrations that ranged from physiologic concentration to higher than pathophysiologic concentration, and we analyzed their expressions of inflammatory cytokines, including tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, interleukin-8, interleukin-12, and migration inhibitory factor.


RESULTS
DL-homocysteine at a marginal physiologic concentration of 2 microg/mL (15 microM) activated monocytes. In addition, DL-homocysteine at the pathophysiologic dose of 25 microg/mL (185 microM) induced mRNA and protein expressions of inflammatory cytokines tumor necrosis factor-alpha, IL-1beta, interleukin-6, interleukin-8, and interleukin-12. Moreover, at the larger dose of 50 microg/mL (370 microM) DL-homocysteine decreased expression of migration inhibitory factor at the mRNA and protein levels.


CONCLUSIONS
These findings suggest that homocysteine may contribute to the initiation and progression of vascular disease by activating monocytes, resulting in the secretion of cytokines that amplify the inflammatory response.
Su
Shu-Jem
SJ
Department of Medical Technology, FooYin University, Kaohsiung, Taiwan.
Huang
Li-Wen
LW
Pai
Ling-Shiu
LS
Liu
Hong-Wen
HW
Chang
Kee-Lung
KL
D000328:Adult; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006710:Homocysteine / Q000097:blood* / Q000494:pharmacology; D006801:Humans; D008263:Macrophage Migration-Inhibitory Factors / Q000037:antagonists & inhibitors*; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000302:isolation & purification / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D014652:Vascular Diseases / Q000097:blood / Q000209:etiology
D015415:Biomarkers; D016207:Cytokines; D008263:Macrophage Migration-Inhibitory Factors; D019384:Nucleic Acid Synthesis Inhibitors; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D006710:Homocysteine; D003609:Dactinomycin; D003513:Cycloheximide