Methotrexate Ameliorates Systemic Inflammation and Septic Associated-Lung Damage in a Cecal Ligation and Puncture Septic Rat Model

Bringué, Josep; Guillamat-Prats, Raquel; Martínez, María Luisa Martínez; Torrents, Eva; Camprubí-Rimblas, Marta; Blanch, Lluís; Artigas, Antonio

doi:10.3390/ijms22179612

Cited by 12 publications

(8 citation statements)

References 64 publications

(75 reference statements)

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“…PRR can interact with PAMP and DAMP, activating the myeloid differentiation primary response protein 88 (MyD88) dependent pathway or Toll/IL-1R domain-containing adaptor-inducing IFN-β (TRIF) dependent pathway ( 166 ). Then, through this signal transduction, downstream nuclear factor κB (NF-κB) ( 167 , 168 ), JAK/STAT ( 169 , 170 ) mitogen-activated protein kinase (MAPK) ( 171 – 173 ) and other signaling pathways ( 174 ) are activated. These pathways upregulate the transcription of genes associated with inflammation, leading to the synthesis and release of various inflammatory molecules.…”

Section: Immunological Mechanisms Of Sepsis-induced Ardsmentioning

confidence: 99%

“…The activation of JAK/STAT signaling pathway has a dual effect on ARDS induced by sepsis. On the one hand, methotrexate (MTX), one inhibitor of the JAK/STAT signaling pathway, was shown to significantly reduce the production of pro-inflammatory cytokines and improve pulmonary inflammatory infiltration ( 169 ). Hence, inhibiting JAK/STAT signaling pathway could alleviate inflammatory lung injury in sepsis.…”

Section: Immunological Mechanisms Of Sepsis-induced Ardsmentioning

confidence: 99%

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Acute respiratory distress syndrome heterogeneity and the septic ARDS subgroup

Xu,

Sheng,

Luo

et al. 2023

Front. Immunol.

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Acute respiratory distress syndrome (ARDS) is an acute diffuse inflammatory lung injury characterized by the damage of alveolar epithelial cells and pulmonary capillary endothelial cells. It is mainly manifested by non-cardiogenic pulmonary edema, resulting from intrapulmonary and extrapulmonary risk factors. ARDS is often accompanied by immune system disturbance, both locally in the lungs and systemically. As a common heterogeneous disease in critical care medicine, researchers are often faced with the failure of clinical trials. Latent class analysis had been used to compensate for poor outcomes and found that targeted treatment after subgrouping contribute to ARDS therapy. The subphenotype of ARDS caused by sepsis has garnered attention due to its refractory nature and detrimental consequences. Sepsis stands as the most predominant extrapulmonary cause of ARDS, accounting for approximately 32% of ARDS cases. Studies indicate that sepsis-induced ARDS tends to be more severe than ARDS caused by other factors, leading to poorer prognosis and higher mortality rate. This comprehensive review delves into the immunological mechanisms of sepsis-ARDS, the heterogeneity of ARDS and existing research on targeted treatments, aiming to providing mechanism understanding and exploring ideas for accurate treatment of ARDS or sepsis-ARDS.

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Section: Immunological Mechanisms Of Sepsis-induced Ardsmentioning

confidence: 99%

Section: Immunological Mechanisms Of Sepsis-induced Ardsmentioning

confidence: 99%

Acute respiratory distress syndrome heterogeneity and the septic ARDS subgroup

Xu,

Sheng,

Luo

et al. 2023

Front. Immunol.

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show abstract

“…In a mouse model of sepsis-induced ALI, the organism may activate the STAT pathway through IL-6 to promote the development of an inflammatory response [ 43 ]. In addition, methotrexate (MTX), an anti-inflammatory agent that inhibits the JAK2/STAT3 pathway, has been shown to ameliorate systemic inflammation and lung injury in a rat model of CLP sepsis [ 44 ]. Inhibition of STAT3 activity by the small molecule inhibitor LLL12 reduces the infiltration of macrophages and inflammatory cells and protected against lipopolysaccharide- (LPS-) induced ALI [ 45 ].…”

Section: Signaling Pathways Related To Ali/ardsmentioning

confidence: 99%

Classic Signaling Pathways in Alveolar Injury and Repair Involved in Sepsis-Induced ALI/ARDS: New Research Progress and Prospect

Chen

et al. 2022

Disease Markers

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Sepsis is a common critical clinical disease with high mortality that can cause approximately 10 million deaths worldwide each year. Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a common clinical complication of sepsis, which occurs primarily as diffuse alveolar injury, hypoxemia, and respiratory distress. The mortality rate of ALI/ARDS is as high as 30%-40%, which greatly endangers human health. Due to the unclear pathogenesis of ALI/ARDS, its treatment is still a worldwide problem. At present, clinical treatment mainly relies on lung-protective ventilation, prone position ventilation, and fluid management. However, there is a lack of effective and specific treatment measures. In recent years, domestic and foreign scholars have committed to basic research on ALI/ARDS, trying to further clarify its pathogenesis and find new targets and methods for the treatment of ALI/ARDS. In this review, we summarize the signaling pathways related to alveolar injury and repair in sepsis-induced ALI/ARDS and their latest research progress. They include the NF-κB, JAK2/STAT3, mitogen-activated protein kinase (MAPK), mTOR, and Notch signaling pathways. Understanding the molecular mechanisms of these signaling pathways in sepsis-induced ALI/ARDS may provide new targets and ideas for the clinical treatment of this disease.

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“…In the cecal ligation puncture (CLP) procedure rat model of ALI, the methotrexate ameliorates systemic inflammation (Bringué et al, 2021). Natural immunosuppressant compounds, derived from plant sources such as release of pro-inflammatory cytokines and chemokines.…”

Section: Jak Inhibitors In the In Vivo Experimental Ards Mouse Modelmentioning

confidence: 99%

JAK-STAT signaling as an ARDS therapeutic target: status and future trends

Zhang

Gao

Yan

et al. 2022

Preprint

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Acute respiratory distress syndrome (ARDS) is an acute respiratory disease which is characterized by non-cardiogenic pulmonary oedema. It has a high mortality rate and lacks effective pharmacotherapy. As the outbreak of COVID worldwide, the mortality of ARDS has increased correspondingly, which makes it urgent to find effective targets and strategies for the treatment of ARDS. Recent clinical trials of Janus kinase (JAK) inhibitors in treating COVID induced ARDS have shown a positive outcome, which makes the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway a potential therapeutic target for treating ARDS. Here, we review the complex cause of ARDS, the molecular pathway of JAK/STAT involved in ARDS pathology, and the progress that has been made in strategies of targeting JAK/STAT to treat ARDS Specially, JAK/STAT signaling directly participates in the progression of ARDS or collude with other pathways to aggravate ARDS. We summarize JAK and STAT inhibitors with ARDS treatment benefits, including inhibitors in clinical trials and pre-clinical studies and natural products, and discuss the side effects of the current JAK inhibitors to reveal the future trends in designing of JAK inhibitors, which will help to develop effective treatment strategies for ARDS in the future.

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Methotrexate Ameliorates Systemic Inflammation and Septic Associated-Lung Damage in a Cecal Ligation and Puncture Septic Rat Model

Cited by 12 publications

References 64 publications

Acute respiratory distress syndrome heterogeneity and the septic ARDS subgroup

Acute respiratory distress syndrome heterogeneity and the septic ARDS subgroup

Classic Signaling Pathways in Alveolar Injury and Repair Involved in Sepsis-Induced ALI/ARDS: New Research Progress and Prospect

JAK-STAT signaling as an ARDS therapeutic target: status and future trends

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