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 val...

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Main Authors: Jian-Li Ma, Peng-Yuan Yang, Yao-Cheng Rui, Ling Lu, Hui Kang, Jing Zhang
Format: Article
Language:English
Published: Elsevier 2007-01-01
Series:Journal of Pharmacological Sciences
Online Access:http://www.sciencedirect.com/science/article/pii/S1347861319343038
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author Jian-Li Ma
Peng-Yuan Yang
Yao-Cheng Rui
Ling Lu
Hui Kang
Jing Zhang
author_facet Jian-Li Ma
Peng-Yuan Yang
Yao-Cheng Rui
Ling Lu
Hui Kang
Jing Zhang
author_sort Jian-Li Ma
collection DOAJ
description 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)-1β and tumor necrosis factor (TNF)-α 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 antiinflammatory therapeutic target through inhibiting pro-inflammatory cytokines and enhancing anti-inflammatory cytokines for the management of atherogenesis. Keywords:: heme oxygenase (HO)-1, hemin, cytokine, macrophage-derived foam cell, atherosclerosis
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spelling doaj.art-bbbc65933fe04dc89970a222acc8829d2022-12-21T17:31:56ZengElsevierJournal of Pharmacological Sciences1347-86132007-01-011033261266Hemin Modulates Cytokine Expressions in Macrophage-Derived Foam Cells via Heme Oxygenase-1 InductionJian-Li Ma0Peng-Yuan Yang1Yao-Cheng Rui2Ling Lu3Hui Kang4Jing Zhang5Department of Pharmacology, School of Pharmacy, Second Military Medical University, No. 325 GuoHe Road, Shanghai 200433, China; First Affiliated Hospital, General Hospital of PLA, No. 51 FuCheng Road, Beijing 100037, ChinaDepartment of Pharmacology, School of Pharmacy, Second Military Medical University, No. 325 GuoHe Road, Shanghai 200433, ChinaDepartment of Pharmacology, School of Pharmacy, Second Military Medical University, No. 325 GuoHe Road, Shanghai 200433, China; Corresponding author. ruiyc@smmu.edu.cnDepartment of Pharmacology, School of Pharmacy, Second Military Medical University, No. 325 GuoHe Road, Shanghai 200433, ChinaDepartment of Pharmacology, School of Pharmacy, Second Military Medical University, No. 325 GuoHe Road, Shanghai 200433, ChinaDepartment of Pharmacology, School of Pharmacy, Second Military Medical University, No. 325 GuoHe Road, Shanghai 200433, ChinaLipid-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)-1β and tumor necrosis factor (TNF)-α 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 antiinflammatory therapeutic target through inhibiting pro-inflammatory cytokines and enhancing anti-inflammatory cytokines for the management of atherogenesis. Keywords:: heme oxygenase (HO)-1, hemin, cytokine, macrophage-derived foam cell, atherosclerosishttp://www.sciencedirect.com/science/article/pii/S1347861319343038
spellingShingle Jian-Li Ma
Peng-Yuan Yang
Yao-Cheng Rui
Ling Lu
Hui Kang
Jing Zhang
Hemin Modulates Cytokine Expressions in Macrophage-Derived Foam Cells via Heme Oxygenase-1 Induction
Journal of Pharmacological Sciences
title Hemin Modulates Cytokine Expressions in Macrophage-Derived Foam Cells via Heme Oxygenase-1 Induction
title_full Hemin Modulates Cytokine Expressions in Macrophage-Derived Foam Cells via Heme Oxygenase-1 Induction
title_fullStr Hemin Modulates Cytokine Expressions in Macrophage-Derived Foam Cells via Heme Oxygenase-1 Induction
title_full_unstemmed Hemin Modulates Cytokine Expressions in Macrophage-Derived Foam Cells via Heme Oxygenase-1 Induction
title_short Hemin Modulates Cytokine Expressions in Macrophage-Derived Foam Cells via Heme Oxygenase-1 Induction
title_sort hemin modulates cytokine expressions in macrophage derived foam cells via heme oxygenase 1 induction
url http://www.sciencedirect.com/science/article/pii/S1347861319343038
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