Review Article

Functional Immunoregulation by Heme Oxygenase 1 in Juvenile Autoimmune Diseases

Author(s): Xueyan Zhang, Shupeng Shi, Jie Shen, Mingyi Zhao* and Qingnan He*

Volume 19, Issue 2, 2019

Page: [110 - 116] Pages: 7

DOI: 10.2174/1566523219666190710092935

Price: $65


An autoimmune disease is an inflammatory condition in which the human body’s immune system attacks normal cells, resulting in decreased and abnormal immune function, which eventually leads to tissue damage or organ dysfunction. In the field of medicine, especially in pediatrics, knowledge about autoimmune diseases is still inadequate. Some common juvenile autoimmune diseases such as Henoch–Schonlein purpura, systemic juvenile idiopathic arthritis, mucocutaneous lymph node syndrome, and autoimmune encephalitis cause considerable public concern. Recent studies revealed that heme oxygenase 1 (HO-1), an enzyme that participates in heme degradation, plays a critical role in the pathogenesis and may regulate autoimmunity. Firstly, it may promote the differentiation of T lymphocytes into CD4+CD25+ regulatory T cells and may be associated with changes in the ratios of cytokines (Th1/Th2 and Th17/Treg) as well. Secondly, HO-1 can regulate the immune system through the secretion of proteins such as transforming growth factors and interleukins. Moreover, increasing the expression of HO-1 can improve vascular function by increasing antioxidant levels. Thus, HO-1 may provide a theoretical basis and guidance for therapeutic management of juvenile autoimmune diseases.

Keywords: Juvenile autoimmune disease, heme oxygenase 1, proinflammatory cytokine, inflammatory cytokine, T lymphocyte, MCLS.

Graphical Abstract
Dunn LL, Midwinter RG, Ni J, Hamid HA, Parish CR, Stocker R. New insights into intracellular locations and functions of heme oxygenase-1. Antioxid Redox Signal 2014; 20(11): 1723-42.
Chen JC, Huang KC, Lin WW. HMG-CoA reductase inhibitors upregulate heme oxygenase-1 expression in murine RAW264.7 macrophages via ERK, p38 MAPK and protein kinase G pathways. Cell Signal 2006; 18(1): 32-9.
[] [PMID: 16214041]
Hamann CR, Egeberg A, Silverberg JI, Gislason G, Skov L, Thyssen JP. Association between parental autoimmune disease and atopic dermatitis in their offspring: A matched case-control study. J Eur Acad Dermatol Venereol 2019; 33(6): 1143-51.
He Z, Li X, Chen H, et al. Nobiletin attenuates lipopolysaccharide/D-galactosamine-induced liver injury in mice by activating the Nrf2 antioxidant pathway and subsequently inhibiting NF-κB-mediated cytokine production. Mol Med Rep 2016; 14(6): 5595-600.
[] [PMID: 27878238]
Weng P, Zhang XT, Sheng Q, et al. Caveolin-1 scaffolding domain peptides enhance anti-inflammatory effect of heme oxygenase-1 through interrupting its interact with caveolin-1. Oncotarget 2017; 8(25): 40104-14.
[] [PMID: 28402952]
Hu X, Li L, Yan S, Li Z. Arsenic trioxide suppresses acute graftversus- host disease by activating the Nrf2/HO-1 pathway in mice. British journal of hematology 2019.
Zhao C, Jiang P, He Z, et al. Dimethyl itaconate protects against lippolysacchride-induced mastitis in mice by activating MAPKs and Nrf2 and inhibiting NF-κB signaling pathways. Microb Pathog 2019; 133103541
[] [PMID: 31100405]
Chen HG, Xie KL, Han HZ, et al. Heme oxygenase-1 mediates the anti-inflammatory effect of molecular hydrogen in LPS-stimulated RAW 264.7 macrophages. Int J Surg 2013; 11(10): 1060-6.
Jiang XP, Huang XL, Yang ZP, et al. Iguratimod ameliorates inflammatory responses by modulating the Th17/Treg paradigm in dextran sulphate sodium-induced murine colitis. Mol Immunol 2018; 93: 9-19.
[] [PMID: 29121519]
Viisanen T, Gazali AM, Ihantola EL, et al. FOXP3+ Regulatory T Cell compartment is altered in children with newly diagnosed Type 1 Diabetes but not in autoantibody-positive at-risk children. Front Immunol 2019; 10: 19.
[] [PMID: 30723474]
Jiang H, Wu X, Zhu H, Xie Y, Tang S, Jiang Y. FOXP3(+)Treg/Th17 cell imbalance in lung tissues of mice with asthma. Int J Clin Exp Med 2015; 8(3): 4158-63.
[PMID: 26064325]
Gomperts E, Belcher JD, Otterbein LE, et al. The role of carbon monoxide and heme oxygenase in the prevention of sickle cell disease vaso-occlusive crises. Am J Hematol 2017; 92(6): 569-82.
[] [PMID: 28378932]
Botto S, Gustin JK, Moses AV. The heme metabolite carbon monoxide facilitates KSHV infection by inhibiting TLR4 signaling in endothelial cells. Front Microbiol 2017; 8: 568.
[] [PMID: 28421060]
Stocker R, Perrella MA. Heme oxygenase-1: A novel drug target for atherosclerotic diseases? Circulation 2006; 114(20): 2178-89.
[] [PMID: 17101869]
Collinson EJ, Wimmer-Kleikamp S, Gerega SK, et al. The yeast homolog of heme oxygenase-1 affords cellular antioxidant protection via the transcriptional regulation of known antioxidant genes. J Biol Chem 2011; 286(3): 2205-14.
[] [PMID: 21081499]
Fall N, Barnes M, Thornton S, et al. Gene expression profiling of peripheral blood from patients with untreated new-onset systemic juvenile idiopathic arthritis reveals molecular heterogeneity that may predict macrophage activation syndrome. Arthritis Rheum 2007; 56(11): 3793-804.
[] [PMID: 17968951]
Mellins ED, Macaubas C, Grom AA. Pathogenesis of systemic juvenile idiopathic arthritis: Some answers, more questions. Nat Rev Rheumatol 2011; 7(7): 416-26.
[] [PMID: 21647204]
Gohar F, Kessel C, Lavric M, Holzinger D, Foell D. Review of biomarkers in systemic juvenile idiopathic arthritis: Helpful tools or just playing tricks? Arthritis Res Ther 2016; 18: 163.
[] [PMID: 27411444]
van den Ham HJ, de Jager W, Bijlsma JW, Prakken BJ, de Boer RJ. Differential cytokine profiles in juvenile idiopathic arthritis subtypes revealed by cluster analysis. Rheumatology 2009; 48(8): 899-905.
[] [PMID: 19478039]
de Jager W, Hoppenreijs EP, Wulffraat NM, Wedderburn LR, Kuis W, Prakken BJ. Blood and synovial fluid cytokine signatures in patients with juvenile idiopathic arthritis: A cross-sectional study. Ann Rheum Dis 2007; 66(5): 589-98.
[] [PMID: 17170049]
Mahmud SA, Binstadt BA. Autoantibodies in the pathogenesis, diagnosis, and prognosis of juvenile idiopathic arthritis. Front Immunol 2019; 9: 3168.
[] [PMID: 30693002]
Tavakolpour S. Towards personalized medicine for patients with autoimmune diseases: Opportunities and challenges. Immunol Lett 2017; 190: 130-8.
[] [PMID: 28797806]
Lei WT, Tsai PL, Chu SH, et al. Incidence and risk factors for recurrent Henoch-Schönlein purpura in children from a 16-year Nationwide database. Pediatr Rheumatol Online J 2018; 16(1): 25.
[] [PMID: 29661187]
Shao X, Jiang C, Li Y, et al. Function of CD4(+) CD25(+) regulatory T cells in Henoch-Schonlein purpura nephritis in children. Zhonghua Er Ke Za Zhi 2014; 52(7): 516-20.
[PMID: 25224057]
Wang Q, Shi YY, Cao M, Dong W, Zhang JB. Role of imbalance between Th17 cells and Treg cells in the pathogenesis of children with Henoch-Schonlein Purpura. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2015; 23(5): 1391-6.
[PMID: 26524044]
Bettelli E, Oukka M, Kuchroo VKTT. (H)-17 cells in the circle of immunity and autoimmunity. Nat Immunol 2007; 8(4): 345-50.
[] [PMID: 17375096]
Afzali B, Lombardi G, Lechler RI, Lord GM. The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease. Clin Exp Immunol 2007; 148(1): 32-46.
[] [PMID: 17328715]
Giacchi V, Sciacca P, Stella I, et al. Assessment of coronary artery intimal thickening in patients with a previous diagnosis of Kawasaki disease by using high resolution transthoracic echocardiography: our experience. BMC Cardiovasc Disord 2014; 14: 106.
[] [PMID: 25139118]
Cho HJ, Yang SI, Kim KH, Kim JN, Kil HR. Cardiovascular risk factors of early atherosclerosis in school-aged children after Kawasaki disease. Korean J Pediatr 2014; 57(5): 217-21.
[] [PMID: 25045363]
Straface E, Marchesi A, Gambardella L, et al. Does oxidative stress play a critical role in cardiovascular complications of Kawasaki disease? Antioxid Redox Signal 2012; 17(10): 1441-6.
[] [PMID: 22578402]
Donovan EL, McCord JM, Reuland DJ, Miller BF, Hamilton KL. Phytochemical activation of Nrf2 protects human coronary artery endothelial cells against an oxidative challenge. Oxid Med Cell Longev 2012.2012132931
[] [PMID: 22685617]
Mizuno K, Toma T, Tsukiji H, et al. Selective expansion of CD16highCCR2- subpopulation of circulating monocytes with preferential production of haem oxygenase (HO)-1 in response to acute inflammation. Clin Exp Immunol 2005; 142(3): 461-70.
[] [PMID: 16297158]
Kelley BP, Patel SC, Marin HL, Corrigan JJ, Mitsias PD, Griffith B. Autoimmune encephalitis: Pathophysiology and imaging review of an overlooked diagnosis. AJNR Am J Neuroradiol 2017; 38(6): 1070-8.
[] [PMID: 28183838]
Spatola M, Dalmau J. Seizures and risk of epilepsy in autoimmune and other inflammatory encephalitis. Curr Opin Neurol 2017; 30(3): 345-53.
[] [PMID: 28234800]
Shen Y, Zhang ZJ, Zhu MD, Jiang BC, Yang T, Gao YJ. Exogenous induction of HO-1 alleviates vincristine-induced neuropathic pain by reducing spinal glial activation in mice. Neurobiol Dis 2015; 79: 100-10.
[] [PMID: 25956228]
Lancaster E. The Diagnosis and treatment of autoimmune encephalitis. J Clin Neurol 2016; 12(1): 1-13.
[] [PMID: 26754777]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy