Synergism of TNF-α and IFN-β triggers human airway epithelial cells death by apoptosis and pyroptosis

Sun, Rui; Jiang, Kaimin; Zeng, Canrong; Zhu, Rui; Chu, Hanyu; Liu, Huiyong; Du, Jingchun

doi:10.1016/j.molimm.2022.12.002

Cited by 15 publications

(10 citation statements)

References 30 publications

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“…It is conceivable that more prolonged incubation times could result in a more pronounced damage phenotype; however, addressing a chronic effect of cytokines for longer times is not feasible in our cell model because of the high cell proliferation rate. Actually, our findings are in contrast with the literature data that describe a synergism of IFNγ plus TNFα as a trigger for apoptosis and pyroptosis in BEAS-2B airway epithelial cells [ 35 ]. Similarly, the same combination of cytokines has been described as an effective approach to induce cell death in cancer cells [ 36 ], and high levels of TNFα and IFNγ are supposed to be responsible for the inflammatory cell death in severe COVID-19 patients [ 28 , 29 ].…”

Section: Discussioncontrasting

confidence: 99%

IRF1 Mediates Growth Arrest and the Induction of a Secretory Phenotype in Alveolar Epithelial Cells in Response to Inflammatory Cytokines IFNγ/TNFα

Recchia Luciani,

Barilli,

Visigalli

et al. 2024

IJMS

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In COVID-19, cytokine release syndrome can cause severe lung tissue damage leading to acute respiratory distress syndrome (ARDS). Here, we address the effects of IFNγ, TNFα, IL-1β and IL-6 on the growth arrest of alveolar A549 cells, focusing on the role of the IFN regulatory factor 1 (IRF1) transcription factor. The efficacy of JAK1/2 inhibitor baricitinib has also been tested. A549 WT and IRF1 KO cells were exposed to cytokines for up to 72 h. Cell proliferation and death were evaluated with the resazurin assay, analysis of cell cycle and cycle-regulator proteins, LDH release and Annexin-V positivity; the induction of senescence and senescence-associated secretory phenotype (SASP) was evaluated through β-galactosidase staining and the quantitation of secreted inflammatory mediators. While IL-1 and IL-6 proved ineffective, IFNγ plus TNFα caused a proliferative arrest in A549 WT cells with alterations in cell morphology, along with the acquisition of a secretory phenotype. These effects were STAT and IRF1-dependent since they were prevented by baricitinib and much less evident in IRF1 KO than in WT cells. In alveolar cells, STATs/IRF1 axis is required for cytokine-induced proliferative arrest and the induction of a secretory phenotype. Hence, baricitininb is a promising therapeutic strategy for the attenuation of senescence-associated inflammation.

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Section: Discussioncontrasting

confidence: 99%

IRF1 Mediates Growth Arrest and the Induction of a Secretory Phenotype in Alveolar Epithelial Cells in Response to Inflammatory Cytokines IFNγ/TNFα

Recchia Luciani,

Barilli,

Visigalli

et al. 2024

IJMS

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“…A previous in vivo study demonstrated that intratracheal TNF-α instillation did not dramatically affect the early apoptotic cell death in lung after LPS exposure [ 138 ]. While Sun et al [ 139 ] recently found that TNF-α significantly enhances IFN-β-mediated apoptosis of airway epithelial cells in vitro. The involvement of TRAIL/TRAILR signaling in apoptosis and lung barrier dysfunction during ARDS has also been described [ 140 ].…”

Section: Molecular Mechanisms and Signaling Pathwaysmentioning

confidence: 99%

Signaling pathways and potential therapeutic targets in acute respiratory distress syndrome (ARDS)

Huang,

Le,

et al. 2024

Respir Res

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Acute respiratory distress syndrome (ARDS) is a common condition associated with critically ill patients, characterized by bilateral chest radiographical opacities with refractory hypoxemia due to noncardiogenic pulmonary edema. Despite significant advances, the mortality of ARDS remains unacceptably high, and there are still no effective targeted pharmacotherapeutic agents. With the outbreak of coronavirus disease 19 worldwide, the mortality of ARDS has increased correspondingly. Comprehending the pathophysiology and the underlying molecular mechanisms of ARDS may thus be essential to developing effective therapeutic strategies and reducing mortality. To facilitate further understanding of its pathogenesis and exploring novel therapeutics, this review provides comprehensive information of ARDS from pathophysiology to molecular mechanisms and presents targeted therapeutics. We first describe the pathogenesis and pathophysiology of ARDS that involve dysregulated inflammation, alveolar-capillary barrier dysfunction, impaired alveolar fluid clearance and oxidative stress. Next, we summarize the molecular mechanisms and signaling pathways related to the above four aspects of ARDS pathophysiology, along with the latest research progress. Finally, we discuss the emerging therapeutic strategies that show exciting promise in ARDS, including several pharmacologic therapies, microRNA-based therapies and mesenchymal stromal cell therapies, highlighting the pathophysiological basis and the influences on signal transduction pathways for their use.

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“…Therefore, an inflammatory condition in the respiratory tract worsens due to the consistent secretion of pro‐inflammatory cytokines (IL‐1β, IL‐18, and TNF‐α) through pyroptosis and necroptosis mechanisms. Finally, further inflammation generated within the entire respiratory tract can damage the integrity of lung parenchyma and epithelial cells 104,105 . TLR3/4 is upregulated during IV infection.…”

Section: Network Of the Inflammasome Cellular Death Pathways In IV In...mentioning

confidence: 99%

“…Finally, further inflammation generated within the entire respiratory tract can damage the integrity of lung parenchyma and epithelial cells. 104,105 TLR3/4 is upregulated during IV infection. Then, RIPK3 is recruited and downstream molecules such as NFƘB, MYD88, and TRIF are activated, resulting in triggering necroptosis pathway.…”

Section: Network Of the Inflammasome Cellular Death Pathways In IV In...mentioning

confidence: 99%

Interaction among inflammasome, PANoptosise, and innate immune cells in infection of influenza virus: Updated review

Wei,

Wang,

Zhou

2023

Immunity Inflam & Disease

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BackgroundInfluenza virus (IV) is a leading cause of respiratory tract infections, eliciting responses from key innate immune cells such as Macrophages (MQs), Neutrophils, and Dendritic Cells (DCs). These cells employ diverse mechanisms to combat IV, with Inflammasomes playing a pivotal role in viral infection control. Cellular death mechanisms, including Pyroptosis, Apoptosis, and Necroptosis (collectively called PANoptosis), significantly contribute to the innate immune response.MethodsIn this updated review, we delve into the intricate relationship between PANoptosis and Inflammasomes within innate immune cells (MQs, Neutrophils, and DCs) during IV infections. We explore the strategies employed by IV to evade these immune defenses and the consequences of unchecked PANoptosis and inflammasome activation, including the potential development of severe complications such as cytokine storms and tissue damage.ResultsOur analysis underscores the interplay between PANoptosis and Inflammasomes as a critical aspect of the innate immune response against IV. We provide insights into IV's various mechanisms to subvert these immune pathways and highlight the importance of understanding these interactions to develop effective antiviral medications.ConclusionA comprehensive understanding of the dynamic interactions between PANoptosis, Inflammasomes, and IV is essential for advancing our knowledge of innate immune responses to viral infections. This knowledge will be invaluable in developing targeted antiviral therapies to combat IV and mitigate potential complications, including cytokine storms and tissue damage.

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Synergism of TNF-α and IFN-β triggers human airway epithelial cells death by apoptosis and pyroptosis

Cited by 15 publications

References 30 publications

IRF1 Mediates Growth Arrest and the Induction of a Secretory Phenotype in Alveolar Epithelial Cells in Response to Inflammatory Cytokines IFNγ/TNFα

IRF1 Mediates Growth Arrest and the Induction of a Secretory Phenotype in Alveolar Epithelial Cells in Response to Inflammatory Cytokines IFNγ/TNFα

Signaling pathways and potential therapeutic targets in acute respiratory distress syndrome (ARDS)

Interaction among inflammasome, PANoptosise, and innate immune cells in infection of influenza virus: Updated review

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