Hydrogen Sulfide Improves Neutrophil Migration and Survival in Sepsis via K<sup>+</sup><sub>ATP</sub>Channel Activation

Spiller, Fernando; Orrico, Maria I. L.; Nascimento, Daniele C.; Czaikoski, Paula Giselle; Souto, Fabrício Oliveira; Alves‐Filho, José C.; Freitas, Aguinaldo de; Carlos, Daniela; Montenegro, Marcelo F.; Neto, Alberto Federman; Ferreira, Sérgio Henrique; Rossi, Marcos A.; Hothersall, John S.; Assreuy, Jamil; Cunha, Fernando

doi:10.1164/rccm.200907-1145oc

Cited by 100 publications

(94 citation statements)

References 42 publications

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“…R-NO, nitroso-compounds; R-S, sulphur-bound-compounds. of mice with sepsis was increased by a pretreatment with H 2 S, which improved leukocyte rolling/adhesion in the mesenteric microcirculation as well as neutrophil migration, reduced bacteremia levels, and prevented hypotension and lung lesions (Spiller et al 2010); pretreatment of oxidised low density lipoprotein with H 2 S destroyed lipid hydroperoxides (Muellner et al 2009); H 2 S pretreatment of isolated cardiomyocytes and an in vivo rat model of myocardial infarction produced potent cardioprotection against lethal ischemia (Pan et al 2006(Pan et al , 2009; pretreatment of brain endothelial cells with H 2 S protected the cells from oxidative damage (Tyagi et al 2009) and pretreatment of mice with H 2 S gas inhalation protected the animals from lethal hypoxia (Blackstone and Roth 2007).…”

Section: Discussionmentioning

confidence: 99%

The hypothesis of the main role of H2S in coupled sulphide-nitroso signalling pathway

Bertova

Čačányiová²,

Kristek³

et al. 2010

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Abstract. As a part of the nitroso signalling pathway, nitroso-compounds serve as stores and carriers of NO; as part of the sulphide signalling pathway, bound sulfane-sulphur compounds serve as stores and carriers of H 2 S. Here we hypothesise a coupled sulphide-nitroso signalling pathway, in which H 2 S plays a main role. H 2 S releases NO from the endogenous S-nitroso-compounds nitrosocysteine, nitroso-acetylcysteine and nitroso-albumin. Relaxation of noradrenaline-precontracted aortic rings by H 2 S is also enhanced in the presence of nitroso-albumin, which may implicate the involvement of the nitroso signalling pathway. Pretreatment of albumin, cysteine, N-acetylcysteine and lipids with H 2 S results in binding of sulphur to these compounds creating thus new-modified sulphur compounds that release NO from nitroso-compounds directly and/or through released H 2 S, which suggests sulphide-nitroso signalling pathway participation. This hypothesis is supported by the observation that the pretreatment of noradrenaline-precontracted aortic rings with H 2 S significantly enhanced relaxation induced by nitroso-glutathione in the absence of H 2 S. We assume that the NO release from nitroso-compounds directly by H 2 S or indirectly by the H 2 S-induced sulphur-bound compounds represents coupled sulphide-nitroso signalling, which may explain some of the numerous biological effects of H 2 S that are shared with NO.

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Section: Discussionmentioning

confidence: 99%

The hypothesis of the main role of H2S in coupled sulphide-nitroso signalling pathway

Bertova

Čačányiová²,

Kristek³

et al. 2010

gpb

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“…A more likely explanation for this difference in proliferative rate resides in the different cellular composition of the sample as the cells from vehicle-treated rats contained more eosinophils and neutrophils and those from ShK-186-treated rats contained more macrophages, and the different cell subsets proliferate at different rates in culture in the absence of exogenous antigens or mitogens. Human and mouse eosinophils and neutrophils express ATP-dependent and K Ca potassium channels, but no currents resembling K V 1.3 were observed in those cells (45)(46)(47)(48). ShK-186 is 100-fold selective for K V 1.3 over the closely related K V 1.1 and 700-fold or more selective for K V 1.3 over all other ion channels tested (11,14,15).…”

Section: Cd45ramentioning

confidence: 97%

Blocking KV1.3 Channels Inhibits Th2 Lymphocyte Function and Treats a Rat Model of Asthma

Koshy

Huq²,

Tanner³

et al. 2014

Journal of Biological Chemistry

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“…2A). The dose range (50-300 lM) was chosen by reference to previous studies (46,47). HAMP expression induced by LPS-CM was markedly suppressed by NaHS pretreatment in a concentration-dependent manner (Fig.…”

Section: H 2 S Attenuates Lps-induced Hepcidin Expression and Regulatmentioning

confidence: 99%

Hydrogen Sulfide Attenuates Inflammatory Hepcidin by Reducing IL-6 Secretion and Promoting SIRT1-Mediated STAT3 Deacetylation

Hong

Wang

Tang

et al. 2016

Antioxidants & Redox Signaling

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Aims: Anemia of inflammation is quite prevalent in hospitalized patients with poor prognosis. Concerns about the effectiveness and safety of iron supplementation have arisen, driving the demand for alternative therapies. Induction of hepatic hepcidin, the master hormone of iron homeostasis, causes anemia under inflammatory conditions. Previous studies indicated that hydrogen sulfide (H 2 S), the third gasotransmitter and a well-known regulator of inflammation, may inhibit the secretion of inflammatory cytokines. We thus investigated the effect of H 2 S on inflammatory hepcidin induction. Results: H 2 S suppressed lipopolysaccharide (LPS)-induced hepcidin production and regulated iron homeostasis in mice by decreasing serum interleukin-6 (IL-6) and Janus kinase 2 ( JAK2)/signal transducer and activator of transcription 3 (STAT3) activation; similar results were obtained in Huh7 cells exposed to conditioned medium from LPS-challenged THP-1 macrophages. Intriguingly, we found H 2 S also attenuated hepcidin levels in Huh7 cells and mouse primary hepatocytes in a sirtuin 1 (SIRT1)-dependent manner. By promoting SIRT1 expression and stabilizing SIRT1-STAT3 interactions, H 2 S ameliorated IL-6-induced STAT3 acetylation, resulting in reduced hepcidin production. Inhibition and silencing of SIRT1 diminished H 2 S-mediated suppression of hepcidin, as opposed to SIRT1 activation and overexpression. Consistent results were observed in vivo. Furthermore, knockout of cystathionine c-lyase (CSE), an endogenous H 2 S synthase, exaggerated inflammatory hepcidin expression in mice. Innovation: For the first time, we elucidated the effects and possible mechanisms of H 2 S on inflammatory hepcidin and established a novel regulatory link between SIRT1 and hepcidin. Conclusion: Our work demonstrates that H 2 S attenuates inflammation-induced hepatic hepcidin via multipathways and suggests new treatment strategies for anemia of inflammation. Antioxid. Redox Signal. 24, 70-83.

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Hydrogen Sulfide Improves Neutrophil Migration and Survival in Sepsis via K⁺_ATPChannel Activation

Abstract: These results showed that H(2)S restores neutrophil migration to the infectious focus and improves survival outcome in severe sepsis by an ATP-dependent K(+) channel-dependent mechanism.

Cited by 100 publications

References 42 publications

The hypothesis of the main role of H2S in coupled sulphide-nitroso signalling pathway

The hypothesis of the main role of H2S in coupled sulphide-nitroso signalling pathway

Blocking KV1.3 Channels Inhibits Th2 Lymphocyte Function and Treats a Rat Model of Asthma

Hydrogen Sulfide Attenuates Inflammatory Hepcidin by Reducing IL-6 Secretion and Promoting SIRT1-Mediated STAT3 Deacetylation

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Hydrogen Sulfide Improves Neutrophil Migration and Survival in Sepsis via K+ATPChannel Activation

Abstract: These results showed that H(2)S restores neutrophil migration to the infectious focus and improves survival outcome in severe sepsis by an ATP-dependent K(+) channel-dependent mechanism.

Cited by 100 publications

References 42 publications

The hypothesis of the main role of H2S in coupled sulphide-nitroso signalling pathway

The hypothesis of the main role of H2S in coupled sulphide-nitroso signalling pathway

Blocking KV1.3 Channels Inhibits Th2 Lymphocyte Function and Treats a Rat Model of Asthma

Hydrogen Sulfide Attenuates Inflammatory Hepcidin by Reducing IL-6 Secretion and Promoting SIRT1-Mediated STAT3 Deacetylation

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Hydrogen Sulfide Improves Neutrophil Migration and Survival in Sepsis via K⁺_ATPChannel Activation