Systemic inflammation up-regulates serum hepcidin in exacerbations and stabile chronic obstructive pulmonary disease

Tandara, Leida; Grubišić, Tihana Žanić; Gudelj, Ivan; Jurišić, Zrinka; Tandara, Marijan; Gugo, Katarina; Mladinov, Suzana; Salamunić, Ilza

doi:10.1016/j.clinbiochem.2015.07.010

Cited by 19 publications

(24 citation statements)

References 33 publications

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“…Our data that IRP2 promotes mitochondrial iron overload in experimental COPD is consistent with previous observations that CS increases iron deposition systemically and in alveolar macrophages from human subjects with COPD 52 , 53 . Such iron deposition may also be consistent with recent reports of anemia being associated with poor clinical and functional outcomes in COPD 54 – 56 and with reports that systemic inflammation in COPD up-regulates serum hepcidin 57 . Excess tissue or more specifically, excess mitochondrial iron may generate hydroxyl radicals that promote inflammation, cell death and oxidative stress 21 , all of which contribute to the pathogenesis of COPD 1 .…”

Section: Discussionsupporting

confidence: 90%

Mitochondrial iron chelation ameliorates cigarette smoke–induced bronchitis and emphysema in mice

Cloonan

Glass

Laucho-Contreras

et al. 2016

Nat Med

209

223

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Chronic obstructive pulmonary disease (COPD) is linked to both cigarette smoking and genetic determinants. We have previously identified iron-responsive element binding protein 2 (IRP2) as an important COPD susceptibility gene, with IRP2 protein increased in the lungs of individuals with COPD. Here we demonstrate that mice deficient in Irp2 were protected from cigarette smoke (CS)-induced experimental COPD. By integrating RIP-Seq, RNA-Seq, gene expression and functional enrichment clustering analysis, we identified IRP2 as a regulator of mitochondrial function in the lung. IRP2 increased mitochondrial iron loading and cytochrome c oxidase (COX), which led to mitochondrial dysfunction and subsequent experimental COPD. Frataxin-deficient mice with higher mitochondrial iron loading had impaired airway mucociliary clearance (MCC) and higher pulmonary inflammation at baseline, whereas synthesis of cytochrome c oxidase (Sco2)-deficient mice with reduced COX were protected from CS-induced pulmonary inflammation and impairment of MCC. Mice treated with a mitochondrial iron chelator or mice fed a low-iron diet were protected from CS-induced COPD. Mitochondrial iron chelation also alleviated CS-impairment of MCC, CS-induced pulmonary inflammation and CS-associated lung injury in mice with established COPD, suggesting a critical functional role and potential therapeutic intervention for the mitochondrial-iron axis in COPD.

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Section: Discussionsupporting

confidence: 90%

Mitochondrial iron chelation ameliorates cigarette smoke–induced bronchitis and emphysema in mice

Cloonan

Glass

Laucho-Contreras

et al. 2016

Nat Med

209

223

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show abstract

“…An association of hepcidin with anemia in CKD/ESKD is however less clear, supported by some 13 but not all studies 12 . In a breast cancer investigation hepcidin was increased but did not correlate with IL-6 14 , and in a chronic obstructive pulmonary disease (COPD) study hepcidin was elevated but did not increase further with acute exacerbations 15 . There was a modest correlation between IL-6 and hepcidin at COPD exacerbation.…”

Section: Discussionmentioning

confidence: 95%

The interleukin-6-hepcidin-hemoglobin circuit in systemic lupus erythematosus flares

Indrakanti

Alvarado

Zhang

et al. 2016

Lupus

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Objective Hepcidin regulates iron availability and may be responsible for the anemia of chronic disease because it is induced by interleukin-6. This study investigated the IL-6-hepcidin-hemoglobin axis in patients with lupus. Methods IL-6 and hepcidin were measured in serial serum samples collected before, during and after lupus flares by specific ELISAs. Results During renal and non-renal SLE flare cycles IL-6 did not predict hepcidin and hepcidin did not predict hemoglobin. When lupus nephritis patients were in remission, IL-6 and hepcidin were correlated, but hepcidin and hemoglobin were not. Conclusion Hepcidin does not contribute significantly to anemia during active lupus.

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“…Over time, elevations in hepcidin resulting from chronic inflammation may not respond appropriately to declining iron stores and may induce a functional ID. Interestingly, patients with COPD may have an inappropriate suppression of hepcidin in response to ID (18,91) and may have less hepcidin expression in severe end-stage disease (91).…”

Section: Increased Iron Loading In Copdmentioning

confidence: 99%

“…These have proved successful in animal models, and several agents are being evaluated in clinical trials for treatment of anemia of cancer and chronic kidney disease (40). However, whereas hepcidin is increased in stable COPD and during acute exacerbations (18,91), patients with severe COPD may have lower hepcidin levels. Further studies are therefore required to more extensively define the role of hepcidin in the development and progression of COPD.…”

Section: Therapeutic Opportunitiesmentioning

confidence: 99%

The “Iron”-y of Iron Overload and Iron Deficiency in Chronic Obstructive Pulmonary Disease

Cloonan

Mumby²,

Adcock³

et al. 2017

Am J Respir Crit Care Med

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Systemic inflammation up-regulates serum hepcidin in exacerbations and stabile chronic obstructive pulmonary disease

Cited by 19 publications

References 33 publications

Mitochondrial iron chelation ameliorates cigarette smoke–induced bronchitis and emphysema in mice

Mitochondrial iron chelation ameliorates cigarette smoke–induced bronchitis and emphysema in mice

The interleukin-6-hepcidin-hemoglobin circuit in systemic lupus erythematosus flares

The “Iron”-y of Iron Overload and Iron Deficiency in Chronic Obstructive Pulmonary Disease

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