Hemin modulates cytokine expressions in macrophage-derived foam cells via heme oxygenase-1 induction.
Lipid-laden foam cells were considered to be targets for therapeutic intervention in atherosclerosis. Several studies proposed new approaches to alter both lipid accumulation and inflammatory responses in macrophages. Finding anti-inflammatory signals during foam cell formation would provide new valid targets for anti-atherosclerotic treatment. The aim of the present study was to see whether oxidized low-density lipoprotein (ox-LDL) can active heme oxygenase (HO)-1 expression level in a human monocyte line, U937 cells, associated with the increase of cytokine secretion. We used hemin (HO-1 activator) and zinc protoporphyrin IX (ZnPP IX, HO-1 inhibitor) to determine the effect of HO-1 on the regulation of cytokine expressions. The results showed that hemin can significantly decrease pro-inflammatory cytokines interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha levels, while enhancing IL-10 production in a dose-dependent manner in U937 foam cells. ZnPP IX did not significantly affect cytokine levels in foam cells. Our present results suggested that HO-1 is an important anti-inflammatory therapeutic target through inhibiting pro-inflammatory cytokines and enhancing anti-inflammatory cytokines for the management of atherogenesis.
Ma
Jian-Li
JL
Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, China.
Yang
Peng-Yuan
PY
Rui
Yao-Cheng
YC
Lu
Ling
L
Kang
Hui
H
Zhang
Jing
J
D045744:Cell Line, Tumor; D016207:Cytokines / Q000032:analysis / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D004797:Enzyme-Linked Immunosorbent Assay; D005487:Foam Cells / Q000187:drug effects* / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D006427:Hemin / Q000494:pharmacology*; D006801:Humans; D008264:Macrophages / Q000166:cytology
D016207:Cytokines; D006427:Hemin; D051547:Heme Oxygenase-1