scholarly journals The Haptoglobin-CD163-Heme Oxygenase-1 Pathway for Hemoglobin Scavenging

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Jens Haugbølle Thomsen ◽  
Anders Etzerodt ◽  
Pia Svendsen ◽  
Søren K. Moestrup
Keyword(s):  
Carbon Monoxide ◽  
Plasma Concentration ◽  
Inflammatory Response ◽  
Heme Oxygenase ◽  
Enzyme System ◽  
Limiting Factor ◽  
Heme Oxygenase 1 ◽  
Future Studies ◽  
Anti Inflammatory ◽  
Inflammatory Effect

The haptoglobin- (Hp-) CD163-heme oxygenase-1 (HO-1) pathway is an efficient captor-receptor-enzyme system to circumvent the hemoglobin (Hb)/heme-induced toxicity during physiological and pathological hemolyses. In this pathway, Hb tightly binds to Hp leading to CD163-mediated uptake of the complex in macrophages followed by lysosomal Hp-Hb breakdown and HO-1-catalyzed conversion of heme into the metabolites carbon monoxide (CO), biliverdin, and iron. The plasma concentration of Hp is a limiting factor as evident during accelerated hemolysis, where the Hp depletion may cause serious Hb-induced toxicity and put pressure on backup protecting systems such as the hemopexin-CD91-HO pathway. The Hp-CD163-HO-1 pathway proteins are regulated by the acute phase mediator interleukin-6 (IL-6), but other regulatory factors indicate that this upregulation is a counteracting anti-inflammatory response during inflammation. The heme metabolites including bilirubin converted from biliverdin have overall an anti-inflammatory effect and thus reinforce the anti-inflammatory efficacy of the Hp-CD163-HO-1 pathway. Future studies of animal models of inflammation should further define the importance of the pathway in the anti-inflammatory response.

scholarly journals Induction of Heme Oxygenase-1 by Sodium 9-Hydroxyltanshinone IIA Sulfonate Derivative Contributes to Inhibit LPS-Mediated Inflammatory Response in Macrophages

2015 ◽  
Vol 36 (4) ◽  
pp. 1316-1330 ◽  
Author(s):  
Xin-Hua Liu ◽  
Xi-Ling Wang ◽  
Hong Xin ◽  
Dan Wu ◽  
Xiao-Ming Xin ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Response ◽  
Heme Oxygenase ◽  
Inos Expression ◽  
Heme Oxygenase 1 ◽  
Zinc Protoporphyrin ◽  
Nuclear Factor ◽  
Anti Inflammatory ◽  
Underlying Mechanisms ◽  
Inflammatory Effect

Background/Aim: Sodium 9-acetoxyltanshinone IIA sulfonate (ZY-1A4), a novel compound derived from sodium 9-hydroxyltanshinone IIA sulfonate, was synthesized with potential biological activities. This study aimed to explore the effects of ZY-1A4 on lipopolysaccharide (LPS)-triggered inflammatory response and the underlying mechanisms. Methods: Activation of RAW264.7 macrophages was induced by LPS. The effects of ZY-1A4 on inducible nitric oxide synthase (iNOS) expression, nitric oxide (NO) generation, nuclear factor-κB (NF-κB) activation, heme oxygenase-1 (HO-1) expression, and nuclear factor-erythroid 2 related factor 2 (Nrf2) pathway were evaluated to elucidate its underlying mechanisms on inflammatory responses. Results: ZY-1A4 concentration-dependently reduced iNOS expression and NO production, and inhibited c-Jun-N-terminal kinase 1/2 (JNK1/2) phosphorylation and NF-κB activation in LPS-stimulated macrophages. In addition, ZY-1A4 concentration- and time-dependently induced HO-1 expression associated with degradation of Kelch-like ECH-associated protein 1 (Keap1) and nuclear translocation of Nrf2, while the effect of ZY-1A4 was abolished by a phosphoinositide 3-kinase (PI3K) inhibitor LY294002. Intriguingly, pharmacological inactivation of HO-1 with zinc protoporphyrin IX reversed anti-inflammatory effect of ZY-1A4, but the anti-inflammatory effect of ZY-1A4 was largely mimicked by HO-1 by-products carbon monoxide and bilirubin. Furthermore, the inhibitory effect of ZY-1A4 on LPS-induced iNOS expression and NO release was abolished by HO-1 siRNA or LY294002. Conclusion: Our results demonstrated that ZY-1A4 suppressed LPS-induced iNOS expression and NO generation via modulation of NF-κB activation and HO-1 expression. This new finding might shed light to the prevention and therapy of cardiovascular diseases.

Heme oxygenase-1 mediates the anti-inflammatory effect of mushroom Phellinus linteus in LPS-stimulated RAW264.7 macrophages

2006 ◽  
Vol 106 (3) ◽  
pp. 364-371 ◽  
Author(s):  
Byung-Chul Kim ◽  
Joung-Woo Choi ◽  
Hye-Young Hong ◽  
Sin-Ae Lee ◽  
Suntaek Hong ◽  
...  
Keyword(s):  
Heme Oxygenase ◽  
Heme Oxygenase 1 ◽  
Phellinus Linteus ◽  
Raw264.7 Macrophages ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Carbon Monoxide-Neuroglobin Axis Targeting Metabolism Against Neuroinflammation

2021 ◽  
Author(s):  
Daniela Dias-Pedroso ◽  
José S. Ramalho ◽  
Vilma A. Sardão ◽  
John G. Jones ◽  
Carlos C. Romão ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Oxygen Consumption ◽  
Inflammatory Response ◽  
Microglial Cell ◽  
Cell Metabolism ◽  
Competent Cell ◽  
Metabolic Shift ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Abstract Microglia are the immune competent cell of the central nervous system (CNS), promoting brain homeostasis and regulating inflammatory response against infection and injury. Chronic or exacerbated neuroinflammation is a cause of damage in several brain pathologies. Endogenous carbon monoxide (CO), produced from the degradation of heme, is described as anti-apoptotic and anti-inflammatory in several contexts, including in the CNS. Neuroglobin (Ngb) is a haemoglobin-homologous protein, which upregulation triggers antioxidant defence and prevents neuronal apoptosis. Thus, we hypothesized a crosstalk between CO and Ngb, in particular, that the anti-neuroinflammatory role of CO in microglia depends on Ngb. A novel CO-releasing molecule (ALF826) based on molybdenum was used for delivering CO in microglial culture.BV-2 mouse microglial cell line was challenged with lipopolysaccharide (LPS) for triggering inflammation, and after 6h ALF826 was added. CO exposure limited inflammation by decreasing inducible nitric oxide synthase (iNOS) expression and the production of nitric oxide (NO) and tumour necrosis factor-a (TNF-a), and by increasing interleukine-10 (IL-10) release. CO-induced Ngb upregulation correlated in time with CO’s anti-inflammatory effect. Moreover, knocking down Ngb reversed the anti-inflammatory effect of CO, suggesting that dependents on Ngb expression. CO-induced Ngb upregulation was independent on ROS signalling, but partially dependent on the transcriptional factor SP1. Finally, microglial cell metabolism is also involved in the inflammatory response. In fact, LPS treatment decreased oxygen consumption in microglia, indicating a switch to glycolysis, which is associated with a proinflammatory. While CO treatment increased oxygen consumption, reverting LPS effect and indicating a metabolic shift into a more oxidative metabolism. Moreover, in the absence of Ngb this phenotype was no longer observed, indicating Ngb is needed for CO’s modulation of microglial metabolism. Finally, the metabolic shift induced by CO did not depend on alteration of mitochondrial population. In conclusion, neuroglobin emerges for the first time as a key player for CO signalling against exacerbated neuroinflammation in microglia.

Anti-inflammatory effect of transduced PEP-1-heme oxygenase-1 in Raw 264.7 cells and a mouse edema model

2011 ◽  
Vol 411 (2) ◽  
pp. 354-359 ◽  
Author(s):  
Soon Won Kwon ◽  
Eun Jeong Sohn ◽  
Dae Won Kim ◽  
Hoon Jae Jeong ◽  
Mi Jin Kim ◽  
...  
Keyword(s):  
Heme Oxygenase ◽  
Raw 264.7 Cells ◽  
Heme Oxygenase 1 ◽  
Raw 264.7 ◽  
Edema Model ◽  
Anti Inflammatory ◽  
Inflammatory Effect
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