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Allergic and Immunological Disorders

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Studies on Pediatric Disorders

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Abstract

The immune system provides effective defense mechanisms to protect hosts from various pathogens and toxic compounds. However, these immunological functions themselves become oxidative stress to hosts. Heme oxygenase (HO) plays a central role in heme metabolism. HO protects cells and organs from injury evoked by various oxidative stresses. A detailed analysis of the first human case of HO-1 deficiency revealed that this enzyme is involved in the protection of multiple tissues and organs. Notably, in vivo studies have shown localized HO-1 production to select cell types, e.g., renal tubular epithelium, hepatic Kupffer cells, vascular endothelium and monocytes/macrophages. In vivo and in vitro studies indicated that sustained HO-1 deficiency results in progressive monocyte dysfunction, unregulated macrophage activation, and endothelial cell dysfunction, leading to a catastrophic systemic inflammatory response syndrome. In addition to conventional immunosuppressive and anti-inflammatory therapies, the novel therapy to induce HO-1 production by pharmacological intervention is promising.

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Abbreviations

AIRE:

Autoimmune regulator gene

CAPS:

Cryopyrin-associated periodic syndrome

CINCA:

Chronic infantile neurological cutaneous and articular syndrome

CO:

Carbon monoxide

FDP:

Fibrinogen degradation product

Hb:

Hemoglobin

HO:

Heme oxygenase

Hp:

Haptoglobin

IFN:

Interferon

LCL:

Lymphoblastoid cell line

LPS:

Lipopolysaccharide

MAPK:

Mitogen-activated protein kinase

MAS:

Macrophage activation syndrome

MetHb:

Methemoglobin

NSAID:

Non-steroidal anti-inflammatory drug

PAMP:

Pathogen-associated molecular pattern

PIC:

Plasmin-α2 plasmin inhibitor complex

RBC:

Red blood cells

sJIA:

Systemic juvenile idiopathic arthritis

TAT:

Thrombin–antithrombin complex

TF:

Tissue factor

TLRs:

Toll-like receptors

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Acknowledgements

The author would like to express his sincere thanks to all the collaborators for the past works. Special thanks are given to the H. Matsukawa and S. Kouraba for their excellent technical assistance.

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Authors and Affiliations

  1. Department of Pediatrics, School of Medicine, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, 920-8641, Japan

    Akihiro Yachie M.D., Ph.D.

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  1. Akihiro Yachie M.D., Ph.D.
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Correspondence to Akihiro Yachie M.D., Ph.D. .

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Editors and Affiliations

  1. Dentistry and Pharmaceutical Sciences Department of Pediatrics, Okayama University Graduate School of Medicine, Okayama, Japan

    Hirokazu Tsukahara

  2. Department of Pediatrics, Kansai Medical University, Osaka, Japan

    Kazunari Kaneko

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Yachie, A. (2014). Allergic and Immunological Disorders. In: Tsukahara, H., Kaneko, K. (eds) Studies on Pediatric Disorders. Oxidative Stress in Applied Basic Research and Clinical Practice. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0679-6_15

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