| Pretreatment with carbon monoxide releasing molecules suppresses hepcidin expression during inflammation and endoplasmic reticulum stress through inhibition of the STAT3 and CREBH pathways. | |
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MedLine Citation:
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PMID: 22262759 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The circulating peptide hormone hepcidin maintains systemic iron homeostasis. Hepcidin production increases during inflammation and as a result of endoplasmic reticulum (ER) stress. Elevated hepcidin levels decrease dietary iron absorption and promote iron sequestration in reticuloendothelial macrophages. Furthermore, increased plasma hepcidin levels cause hypoferremia and the anemia associated with chronic diseases. The signal transduction pathways that regulate hepcidin during inflammation and ER stress include the IL-6-dependent signal transducer and activator of transcription-3 (STAT-3) pathway, and the unfolded protein response-associated cyclic AMP response element-binding protein-H (CREBH) pathway, respectively. We show that carbon monoxide (CO) suppresses hepcidin expression elicited by IL-6 and ER-stress agents by inhibiting STAT-3 phosphorylation and CREBH maturation, respectively. The inhibitory effect of CO on IL-6-inducible hepcidin expression is dependent upon the suppressor of cytokine signaling (SOCS)-3 protein. Induction of ER stress in mice resulted in increased hepatic and serum hepcidin. CO administration inhibited ER stress-induced hepcidin expression in vivo. Furthermore, ER stress caused iron accumulation in splenic macrophages, which could be prevented by CO. Our findings suggest novel anti-inflammatory therapeutic applications for CO, as well as therapeutic targets for the amelioration of anemia in the hypoferremic condition associated with chronic inflammatory and metabolic diseases. |
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Authors:
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Da-Yong Shin; Jihwa Chung; Yeonsoo Joe; Hyun-Ock Pae; Ki Churl Chang; Gyeong Jae Cho; Stefan W Ryter; Hun-Taeg Chung |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-19 |
Journal Detail:
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Title: Blood Volume: - ISSN: 1528-0020 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-20 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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School of Biological Sciences, University of Ulsan, Meta-Inflammation Basic Research Laboratory, Ulsan, Korea, Republic of; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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