Induced disruption of the iron-regulatory hormone hepcidin inhibits acute inflammatory hypoferremia
Withdrawal of iron from serum (hypoferremia) is a conserved innate immune antimicrobial strategy that can withhold this critical nutrient from invading pathogens, impairing their growth. Hepcidin (Hamp1) is the master regulator of iron and its expression is induced by inflammation. Mice...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Journal article |
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Karger
2016
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| _version_ | 1826262497399668736 |
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| author | Armitage, A Lim, P Frost, J Pasricha, S Soilleux, E Evans, E Morovat, A Santos, A Diaz, R Biggs, D Davies, B Gileadi, U Robbins, P Lakhal-Littleton, S Drakesmith, A |
| author_facet | Armitage, A Lim, P Frost, J Pasricha, S Soilleux, E Evans, E Morovat, A Santos, A Diaz, R Biggs, D Davies, B Gileadi, U Robbins, P Lakhal-Littleton, S Drakesmith, A |
| author_sort | Armitage, A |
| collection | OXFORD |
| description | Withdrawal of iron from serum (hypoferremia) is a conserved innate immune antimicrobial strategy that can withhold this critical nutrient from invading pathogens, impairing their growth. Hepcidin (Hamp1) is the master regulator of iron and its expression is induced by inflammation. Mice lacking Hamp1 from birth rapidly accumulate iron and are susceptible to infection by blooddwelling siderophilic bacteria such as Vibrio vulnificus. In order to study the innate immune role of hepcidin against a background of normal iron status, we developed a transgenic mouse model of tamoxifen-sensitive conditional Hamp1 deletion (termed iHamp1-KO mice). These mice attain adulthood with iron status indistinguishable from littermate controls. Hamp1 disruption and the consequent decline of serum hepcidin concentrations occurred within hours of a single tamoxifen dose. We found that the TLR ligands LPS and Pam3CSK4 and heat-killed Brucella abortus caused equivalent induction of inflammation in control and iHamp1-KO mice. Pam3CSK4 and Brucella abortus only caused a drop in serum iron in control mice, while hypoferremia due to LPS was evident but substantially blunted in iHamp1-KO mice. Our results characterize a powerful new model of rapidly inducible hepcidin disruption, and demonstrate the critical contribution of hepcidin to the hypoferremia of inflammation. |
| first_indexed | 2024-03-06T19:37:06Z |
| format | Journal article |
| id | oxford-uuid:1f69698a-9936-4130-b4d3-f776f5803551 |
| institution | University of Oxford |
| last_indexed | 2024-03-06T19:37:06Z |
| publishDate | 2016 |
| publisher | Karger |
| record_format | dspace |
| spelling | oxford-uuid:1f69698a-9936-4130-b4d3-f776f58035512022-03-26T11:21:45ZInduced disruption of the iron-regulatory hormone hepcidin inhibits acute inflammatory hypoferremiaJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:1f69698a-9936-4130-b4d3-f776f5803551Symplectic Elements at OxfordKarger2016Armitage, ALim, PFrost, JPasricha, SSoilleux, EEvans, EMorovat, ASantos, ADiaz, RBiggs, DDavies, BGileadi, URobbins, PLakhal-Littleton, SDrakesmith, AWithdrawal of iron from serum (hypoferremia) is a conserved innate immune antimicrobial strategy that can withhold this critical nutrient from invading pathogens, impairing their growth. Hepcidin (Hamp1) is the master regulator of iron and its expression is induced by inflammation. Mice lacking Hamp1 from birth rapidly accumulate iron and are susceptible to infection by blooddwelling siderophilic bacteria such as Vibrio vulnificus. In order to study the innate immune role of hepcidin against a background of normal iron status, we developed a transgenic mouse model of tamoxifen-sensitive conditional Hamp1 deletion (termed iHamp1-KO mice). These mice attain adulthood with iron status indistinguishable from littermate controls. Hamp1 disruption and the consequent decline of serum hepcidin concentrations occurred within hours of a single tamoxifen dose. We found that the TLR ligands LPS and Pam3CSK4 and heat-killed Brucella abortus caused equivalent induction of inflammation in control and iHamp1-KO mice. Pam3CSK4 and Brucella abortus only caused a drop in serum iron in control mice, while hypoferremia due to LPS was evident but substantially blunted in iHamp1-KO mice. Our results characterize a powerful new model of rapidly inducible hepcidin disruption, and demonstrate the critical contribution of hepcidin to the hypoferremia of inflammation. |
| spellingShingle | Armitage, A Lim, P Frost, J Pasricha, S Soilleux, E Evans, E Morovat, A Santos, A Diaz, R Biggs, D Davies, B Gileadi, U Robbins, P Lakhal-Littleton, S Drakesmith, A Induced disruption of the iron-regulatory hormone hepcidin inhibits acute inflammatory hypoferremia |
| title | Induced disruption of the iron-regulatory hormone hepcidin inhibits acute inflammatory hypoferremia |
| title_full | Induced disruption of the iron-regulatory hormone hepcidin inhibits acute inflammatory hypoferremia |
| title_fullStr | Induced disruption of the iron-regulatory hormone hepcidin inhibits acute inflammatory hypoferremia |
| title_full_unstemmed | Induced disruption of the iron-regulatory hormone hepcidin inhibits acute inflammatory hypoferremia |
| title_short | Induced disruption of the iron-regulatory hormone hepcidin inhibits acute inflammatory hypoferremia |
| title_sort | induced disruption of the iron regulatory hormone hepcidin inhibits acute inflammatory hypoferremia |
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