Carbon monoxide ameliorates lipopolysaccharide-induced acute lung injury via inhibition of alveolar macrophage pyroptosis

Xu, Weijie; Huang, Xiangfeng; Li, Wei; Qian, Gang; Zhou, Beiye; Wang, Xiaofei

doi:10.1538/expanim.22-0023

Cited by 5 publications

(3 citation statements)

References 32 publications

(32 reference statements)

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“…In doing so, RAW264.7 and HeLa cells were treated with CORM-2 or CORM-3 for 6 h at two concentrations (50 and 25 μM). Similar concentrations have widely used in literature studies. − CDDO-Me was chosen as a positive control due to its known ability to induce HO-1 by activating Nrf2 through binding to Keap1. , We opted not to use hemin as a positive control for HO-1 induction because it is also a substrate for HO. We sought to avoid the possible complication due to an increased supply of the substrate for HO, thus increasing the level of CO production.…”

Section: Resultsmentioning

confidence: 99%

“…To the best of our knowledge, the link between CO and HO-1 induction has never been truly authenticated in a cell culture with rigorous side-by-side comparisons. Third, we note that the reported inference of HO-1 induction effects by exogenous CO in cell culture largely derives from experiments using transition metal-based CORMs. − The first reported case of the ability of CO to induce HO-1 expression utilized CORM-2 and CORM-3 and their “CO-depleted” or “inactivated” form (iCORMs) as negative controls in cell culture . However, the study did not specifically conclude that CO was able to induce HO-1, at least at the concentration of CORMs (less than 100 μM) used in the studies.…”

Section: Introductionmentioning

confidence: 98%

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On the Question of CO’s Ability to Induce HO-1 Expression in Cell Culture: A Comparative Study Using Different CO Sources

Yang,

Mao,

Wang

2024

ACS Chem. Biol.

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With the recognition of the endogenous signaling roles and pharmacological functions of carbon monoxide (CO), there is an increasing need to understand CO's mechanism of actions. Along this line, chemical donors have been introduced as CO surrogates for ease of delivery, dosage control, and sometimes the ability to target. Among all of the donors, two ruthenium− carbonyl complexes, CORM-2 and -3, are arguably the most commonly used tools for about 20 years in studying the mechanism of actions of CO. Largely based on data using these two CORMs, there has been a widely accepted inference that the upregulation of heme oxygenase-1 (HO-1) expression is one of the key mechanisms for CO's actions. However, recent years have seen reports of very pronounced chemical reactivities and CO-independent activities of these CORMs. We are interested in examining this question by conducting comparative studies using CO gas, CORM-2/-3, and organic CO donors in RAW264.7, HeLa, and HepG2 cell cultures. CORM-2 and CORM-3 treatment showed significant dose-dependent induction of HO-1 compared to "controls," while incubation for 6 h with 250−500 ppm CO gas did not increase the HO-1 protein expression and mRNA transcription level. A further increase of the CO concentration to 5% did not lead to HO-1 expression either. Additionally, we demonstrate that CORM-2/-3 releases minimal amounts of CO under the experimental conditions. These results indicate that the HO-1 induction effects of CORM-2/-3 are not attributable to CO. We also assessed two organic CO prodrugs, BW-CO-103 and BW-CO-111. BW-CO-111 but not BW-CO-103 dose-dependently increased HO-1 levels in RAW264.7 and HeLa cells. We subsequently studied the mechanism of induction with an Nrf2-luciferase reporter assay, showing that the HO-1 induction activity is likely due to the activation of Nrf2 by the CO donors. Overall, CO alone is unable to induce HO-1 or activate Nrf2 under various conditions in vitro. As such, there is no evidence to support attributing the HO-1 induction effect of the CO donors such as CORM-2/-3 and BW-CO-111 in cell culture to CO. This comparative study demonstrates the critical need to consider possible CO-independent effects of a chemical CO donor before attributing the observed biological effects to CO. It is also important to note that such in vitro results cannot be directly extrapolated to in vivo studies because of the increased level of complexity and the likelihood of secondary and/or synergistic effects in the latter.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

On the Question of CO’s Ability to Induce HO-1 Expression in Cell Culture: A Comparative Study Using Different CO Sources

Yang,

Mao,

Wang

2024

ACS Chem. Biol.

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“…Other literature has also mentioned the use of CO in the treatment of lung injury ( 174 ). However, treatment with toxic CO requires careful determination of therapeutic concentration.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-6 and pulmonary hypertension: from physiopathology to therapy

et al. 2023

Front. Immunol.

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Pulmonary hypertension (PH) is a progressive, pulmonary vascular disease with high morbidity and mortality. Unfortunately, the pathogenesis of PH is complex and remains unclear. Existing studies have suggested that inflammatory factors are key factors in PH. Interleukin-6 (IL-6) is a multifunctional cytokine that plays a crucial role in the regulation of the immune system. Current studies reveal that IL-6 is elevated in the serum of patients with PH and it is negatively correlated with lung function in those patients. Since IL-6 is one of the most important mediators in the pathogenesis of inflammation in PH, signaling mechanisms targeting IL-6 may become therapeutic targets for this disease. In this review, we detailed the potential role of IL-6 in accelerating PH process and the specific mechanisms and signaling pathways. We also summarized the current drugs targeting these inflammatory pathways to treat PH. We hope that this study will provide a more theoretical basis for targeted treatment in patients with PH in the future.

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TrxR1 is involved in the activation of Caspase-11 by regulating the oxidative-reductive status of Trx-1

Bai,

Zhou,

et al. 2024

Redox Biology

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Carbon monoxide ameliorates lipopolysaccharide-induced acute lung injury via inhibition of alveolar macrophage pyroptosis

Abstract: Carbon monoxide ameliorates LPS-induced acute lung injury via inhibition of alveolar macrophage pyroptosisShort Title: Carbon monoxide inhibits pyroptosis

Cited by 5 publications

References 32 publications

On the Question of CO’s Ability to Induce HO-1 Expression in Cell Culture: A Comparative Study Using Different CO Sources

On the Question of CO’s Ability to Induce HO-1 Expression in Cell Culture: A Comparative Study Using Different CO Sources

Interleukin-6 and pulmonary hypertension: from physiopathology to therapy

TrxR1 is involved in the activation of Caspase-11 by regulating the oxidative-reductive status of Trx-1

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