Oxidant stress responses in influenza virus pneumonia: gene expression and transcription factor activation

1996 ◽  
Vol 271 (3) ◽  
pp. L383-L391 ◽  
Author(s):  
A. M. Choi ◽  
K. Knobil ◽  
S. L. Otterbein ◽  
D. A. Eastman ◽  
D. B. Jacoby
Keyword(s):  
Influenza Virus ◽  
Viral Infection ◽  
Heme Oxygenase ◽  
Stress Responses ◽  
Oxidant Stress ◽  
Regulatory Proteins ◽  
Heme Oxygenase 1 ◽  
Nf Kappa B ◽  
Transcriptional Regulatory ◽  
Genes Encoding

The pathogenesis of influenza virus infections of the lungs is in part mediated by oxidative stress. Such infections might therefore be expected to induce expression of stress-response genes and genes encoding antioxidant enzymes and to activate transcriptional regulatory proteins. Mice (C57B1/6 and C3H/HeJ) were infected intranasally with influenza virus A/PR/8/34 (H1N1). Expression of the genes encoding the antioxidant enzymes manganese superoxide dismutase (Mn- SOD), indoleamine-2, 3-dioxygenase (IDO), heme oxygenase-1, and glutathione peroxidase were increased in the lungs of virus-infected animals. Cu/ZnSOD and catalase mRNA were not induced by viral infection. Activation of the transcriptional regulatory proteins AP-1, C/EBP, and NF-kappa B (which are known to be affected by oxidant stress) was demonstrated by electrophoretic mobility shift assay after viral infection. In the case of MnSOD, despite increased gene expression enzyme activity was not increased. In contrast, for heme oxygenase-1 both mRNA and activity were increased. C3H/ HeJ and C57B1/6 mice, which are known to have different responses to other types of oxidant stress, also differed in their responses to viral infection. Induction of heme oxygenase-1 expression was greater in C57B1/6 mice than in C3H/ HeJ mice, although inhibiting this enzyme did not alter virus-induced mortality. In contrast, IDO was more strongly induced in C3H/HeJ mice. Activation of NF-kappa B was much more marked in C57B1/6 mice than in C3H/HeJ mice. Although virus replication and inflammatory responses were equivalent in the two strains, lung injury (as measured by wet-to-dry wt ratios) and mortality were greater in C3H/HeJ mice than in C57B1/6 mice, a difference that may be related to differing oxidant stress responses. Thus influenza pneumonia causes an oxidant stress response in the lungs, the nature of which is determined in part by the genetic background of the host.

scholarly journals DMO-CAP inhibits influenza virus replication by activating heme oxygenase-1-mediated IFN response

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Ming Zhong ◽  
Huiqiang Wang ◽  
Linlin Ma ◽  
Haiyan Yan ◽  
Shuo Wu ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Replication ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1 ◽  
Influenza Virus Replication

scholarly journals Antidiabetic Potential of the Heme Oxygenase-1 Inducer Curcumin Analogues

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Yong Son ◽  
Ju Hwan Lee ◽  
Yong-Kwan Cheong ◽  
Hun-Taeg Chung ◽  
Hyun-Ock Pae
Keyword(s):  
Oxidative Stress ◽  
Er Stress ◽  
Heme Oxygenase ◽  
Stress Responses ◽  
Therapeutic Potential ◽  
Heme Oxygenase 1 ◽  
Low Grade ◽  
Cellular Protection ◽  
Inflammatory Stress ◽  
Curcumin Analogues

Although there is a therapeutic treatment to combat diabetes, the identification of agents that may deal with its more serious aspects is an important medical field for research. Diabetes, which contributes to the risk of cardiovascular disease, is associated with a low-grade chronic inflammation (inflammatory stress), oxidative stress, and endoplasmic reticulum (ER) stress. Because the integration of these stresses is critical to the pathogenesis of diabetes, agents and cellular molecules that can modulate these stress responses are emerging as potential targets for intervention and treatment of diabetic diseases. It has been recognized that heme oxygenase-1 (HO-1) plays an important role in cellular protection. Because HO-1 can reduce oxidative stress, inflammatory stress, and ER stress, in part by exerting antioxidant, anti-inflammatory, and antiapoptotic effects, HO-1 has been suggested to play important roles in pathogenesis of diabetes. In the present review, we will explore our current understanding of the protective mechanisms of HO-1 in diabetes and present some emerging therapeutic options for HO-1 expression in treating diabetic diseases, together with the therapeutic potential of curcumin analogues that have their ability to induce HO-1 expression.

scholarly journals Neuroprotective and Anti-Inflammatory Effects of Kuwanon C from Cudrania tricuspidata Are Mediated by Heme Oxygenase-1 in HT22 Hippocampal Cells, RAW264.7 Macrophage, and BV2 Microglia

2020 ◽  
Vol 21 (14) ◽  
pp. 4839 ◽  
Author(s):  
Wonmin Ko ◽  
Chi-Su Yoon ◽  
Kwan-Woo Kim ◽  
Hwan Lee ◽  
Nayeon Kim ◽  
...  
Keyword(s):  
Heme Oxygenase ◽  
Stress Responses ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Neuroprotective Effects ◽  
Bv2 Cells ◽  
Bv2 Microglia ◽  
Anti Inflammatory ◽  
Nrf2 Expression ◽  
Raw264.7 Macrophage

Heme oxygenase (HO)-1 is a detoxifying phase II enzyme that plays a role in both inflammatory and oxidative stress responses. Curdrania tricuspidata is widespread throughout East Asia and is used as a therapeutic agent in traditional medicine. We investigated whether treatment with sixteen flavonoid or xanthone compounds from C. tricuspidata could induce HO-1 expression in HT22 hippocampal cells, RAW264.7 macrophage, and BV2 microglia. In these compounds, kuwanon C showed the most remarkable HO-1 expression effects. In addition, treatment with kuwanon C reduced cytoplasmic nuclear erythroid 2-related factor (Nrf2) expression and increased Nrf2 expression in the nucleus. Significant inhibition of glutamate-induced oxidative injury and induction of reactive oxygen species (ROS) occurred when HT22 hippocampal cells were pretreated with kuwanon C. The levels of inflammatory mediator and cytokine, which increased following lipopolysaccharide (LPS) stimulation, were suppressed in RAW264.7 macrophage and BV2 microglia after kuwanon C pretreatment. Kuwanon C also attenuated p65 DNA binding and translocation into the nucleus in LPS-induced RAW264.7 and BV2 cells. The anti-inflammatory, anti-neuroinflammatory, and neuroprotective effects of kuwanon C were reversed when co-treatment with HO-1 inhibitor of tin protoporphyrin-IX (SnPP). These results suggest that the neuroprotective and anti-inflammatory effects of kuwanon C are regulated by HO-1 expression.

Quercetin protects against pulmonary oxidant stress via heme oxygenase-1 induction in lung epithelial cells

2012 ◽  
Vol 417 (1) ◽  
pp. 169-174 ◽  
Author(s):  
Yuta Hayashi ◽  
Miyoko Matsushima ◽  
Toshinobu Nakamura ◽  
Masataka Shibasaki ◽  
Naozumi Hashimoto ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Heme Oxygenase ◽  
Oxidant Stress ◽  
Lung Epithelial Cells ◽  
Heme Oxygenase 1 ◽  
Lung Epithelial

scholarly journals Myeloid heme oxygenase–1 regulates innate immunity and autoimmunity by modulating IFN-β production

2009 ◽  
Vol 206 (5) ◽  
pp. 1167-1179 ◽  
Author(s):  
Sotiria Tzima ◽  
Panayiotis Victoratos ◽  
Ksanthi Kranidioti ◽  
Maria Alexiou ◽  
George Kollias
Keyword(s):  
Heme Oxygenase ◽  
Target Genes ◽  
Heme Oxygenase 1 ◽  
Immune Functions ◽  
Cell Reactivity ◽  
Direct Function ◽  
Genes Encoding ◽  
T Cell Reactivity ◽  
Immune Pathway ◽  
Antigen Presenting

Heme oxygenase–1 (HO-1) is a key cytoprotective, antioxidant, and antiinflammatory molecule. The pathophysiological functions of HO-1 have been associated with its enzymatic activities in heme catabolism. We have examined the immune functions of HO-1 by its conditional ablation in myeloid cells (HO-1M-KO mice). We demonstrate that myeloid HO-1 is required for the activation of interferon (IFN) regulatory factor (IRF) 3 after Toll-like receptor 3 or 4 stimulation, or viral infection. HO-1–deficient macrophages show reduced expression of IFN-β and of primary IRF3 target genes encoding RANTES, IP-10 and MCP-1. In the presence of polyI:C, myeloid HO-1 knockout mice infected with Listeria monocytogenes, a model dependent on IFN-β production, showed enhanced bacterial clearance and survival, whereas control mice succumbed to infection. Moreover, after induction of experimental autoimmune encephalomyelitis, mice with myeloid-specific HO-1 deficiency developed a higher incidence and an exacerbated, nonremitting clinical disease correlating with persistent activation of antigen-presenting cells, enhanced infiltration of Th17 cells, and a nonregressing myelin-specific T cell reactivity. Notably, these defects were rectified by exogenous administration of IFN-β, confirming that HO-1 functions directly upstream of this critical immune pathway. These results uncover a novel direct function for myeloid HO-1 in the regulation of IFN-β production, establishing HO-1 as a critical early mediator of the innate immune response.

Characterization of a Heme Oxygenase–1 from Tobacco That Is Involved in Some Abiotic Stress Responses

2012 ◽  
Vol 173 (2) ◽  
pp. 113-123 ◽  
Author(s):  
Qi-Jiang Jin ◽  
Jian-Fei Feng ◽  
Ya Sun ◽  
Wei-Ti Cui ◽  
Bin Han ◽  
...  
Keyword(s):  
Abiotic Stress ◽  
Heme Oxygenase ◽  
Stress Responses ◽  
Heme Oxygenase 1

Heme Oxygenase 1 Deficiency Compromises Stress Responses of Hematopoietic Stem Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1353-1353
Author(s):  
Yu-An Cao ◽  
Amy J. Wagers ◽  
Holger Karsunky ◽  
Hui Zhao ◽  
Robert Reeves ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Heme Oxygenase ◽  
Stress Responses ◽  
Mitogen Activated Protein Kinase ◽  
Heme Oxygenase 1 ◽  
Repeated Treatment ◽  
Wild Type ◽  
Self Renewal ◽  
Hematopoietic Stem

Abstract Hematopoietic stem cells (HSCs) must be able to balance their self-renewal and differentiation activities in order to preserve their compartment in response to hematopoietic insults for efficient and life-long hematopoiesis while ensuring sufficient blood production to meet the increased hematopoietic demand. Mechanism(s) that regulate this balance during stress hematopoiesis remain to be fully understood. Heme oxygenase 1 (HO-1) is an important stress-inducible protein and a key enzyme of heme degradation that produces iron, bilirubin, and carbon monoxide (CO). CO is a gaseous regulator of cellular responses to a variety of insults. HO-1 deficiency results in reduced stress defense due to inadequate levels of its products. We report here that mice lacking one allele of HO-1 (HO-1−/+ mice) recovered more rapidly from myelotoxic injury and that sufficient HO-1−/+ bone marrow (BM) transplants engrafted lethally irradiated hosts with accelerated kinetics. These effects of HO-1 deficiency on regenerative hematopoiesis were associated with accelerated cell division of lineage-depleted (lin-) Sca-1+ cells. However, in other experimental settings, the converse can be seen in HO-1 deficiency. Repeated treatment of HO-1−/+ mice with 5-FU significantly reduced the number of HSCs in the marrow, relative to wild-type animals, and following adoptive transfer, the HO-1−/+ HSC compartment was smaller compared to that of HO-1+/+ in recipient animals. As a consequence, limited numbers of HO-1−/+ BM cells failed to provide adequate radio-protection of lethally irradiated recipients, and HO-1−/+ HSCs showed significantly compromised capacity to serially repopulate myeloablated hosts. We also noted that expression levels of the cyclin-dependent kinase inhibitor p21Cip/WAF1 were lower in lin- HO-1−/+ BM cells in contrast to that in HO-1+/+ cells under steady-state conditions, and that p38 mitogen-activated protein kinase (p38MAPK) was insufficiently activated in HO-1−/+ multipotent progenitors (MPPs) after heme challenge, compared to that in wild-type MPPs. We propose a model wherein HO-1 plays an intracellular regulatory and cyto-protective role in maintaining HSC compartment, especially during stress hematopoiesis. It follows that reduced levels of p38MAPK activation, presumably due to insufficient production of CO when HO-1 is deficient, result in accelerated proliferation of MPPs. This would potentially skew the balance between self-renewal and differentiation of HSC and deplete the primitive cell compartment, leading to ultimate hematopoietic exhaustion.

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