Pyroptosis-induced inflammation and tissue damage

Vasudevan, Swathy O.; Behl, Bharat; Rathinam, Vijay

doi:10.1016/j.smim.2023.101781

Cited by 33 publications

(12 citation statements)

References 105 publications

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“…Small DAMPs such as eCIRP (17-19 kDa) are then released through GSDMD’s pores along with IL-1β and IL-18 ( 100 , 101 ). The release of larger DAMPs, such as HMGB1, can ensue when irreversible GSDMD pores cause terminal cell rupture ( 102 , 103 ).…”

Section: Mechanisms Of Damp Release – Passive Pathwaysmentioning

confidence: 99%

DAMPs and radiation injury

Yamaga,

Aziz,

Murao

et al. 2024

Front. Immunol.

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The heightened risk of ionizing radiation exposure, stemming from radiation accidents and potential acts of terrorism, has spurred growing interests in devising effective countermeasures against radiation injury. High-dose ionizing radiation exposure triggers acute radiation syndrome (ARS), manifesting as hematopoietic, gastrointestinal, and neurovascular ARS. Hematopoietic ARS typically presents with neutropenia and thrombocytopenia, while gastrointestinal ARS results in intestinal mucosal injury, often culminating in lethal sepsis and gastrointestinal bleeding. This deleterious impact can be attributed to radiation-induced DNA damage and oxidative stress, leading to various forms of cell death, such as apoptosis, necrosis and ferroptosis. Damage-associated molecular patterns (DAMPs) are intrinsic molecules released by cells undergoing injury or in the process of dying, either through passive or active pathways. These molecules then interact with pattern recognition receptors, triggering inflammatory responses. Such a cascade of events ultimately results in further tissue and organ damage, contributing to the elevated mortality rate. Notably, infection and sepsis often develop in ARS cases, further increasing the release of DAMPs. Given that lethal sepsis stands as a major contributor to the mortality in ARS, DAMPs hold the potential to function as mediators, exacerbating radiation-induced organ injury and consequently worsening overall survival. This review describes the intricate mechanisms underlying radiation-induced release of DAMPs. Furthermore, it discusses the detrimental effects of DAMPs on the immune system and explores potential DAMP-targeting therapeutic strategies to alleviate radiation-induced injury.

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Section: Mechanisms Of Damp Release – Passive Pathwaysmentioning

confidence: 99%

DAMPs and radiation injury

Yamaga,

Aziz,

Murao

et al. 2024

Front. Immunol.

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“…Inflammatory cytokines, such as IL-1β and IL-18, which are released during pyroptosis, are also key players in tissue inflammation, tumor immunity, and cancer progression [ 162 – 164 ]. In addition, several studies have investigated the activity of inflammatory cytokines in CAFs.…”

Section: Effects Of Rcd On Cafsmentioning

confidence: 99%

Crosstalk between cancer-associated fibroblasts and regulated cell death in tumors: insights into apoptosis, autophagy, ferroptosis, and pyroptosis

Chen,

Liu,

Lin

et al. 2024

Cell Death Discov.

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Cancer-associated fibroblasts (CAFs), the main stromal component of the tumor microenvironment (TME), play multifaceted roles in cancer progression through paracrine signaling, exosome transfer, and cell interactions. Attractively, recent evidence indicates that CAFs can modulate various forms of regulated cell death (RCD) in adjacent tumor cells, thus involving cancer proliferation, therapy resistance, and immune exclusion. Here, we present a brief introduction to CAFs and basic knowledge of RCD, including apoptosis, autophagy, ferroptosis, and pyroptosis. In addition, we further summarize the different types of RCD in tumors that are mediated by CAFs, as well as the effects of these modes of RCD on CAFs. This review will deepen our understanding of the interactions between CAFs and RCD and might offer novel therapeutic avenues for future cancer treatments.

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“…GSDMD is a critical regulator of pro-inflammatory cytokine secretion by immune cells, and recent evidence suggests a pivotal modulatory role for GSDMD in the pathogenesis of sepsis. 241 , 342 Although various sensors and mediators activate pyroptosis, the pore-forming activity of GSDMD-NT emerges as a compelling therapeutic target, as it is a universal terminal step required for pyroptosis and the secretion of pro-inflammatory cytokines in response to pathogenic or danger-induced signals. GSDMD inhibition or inactivation does prevent lethal bacterial sepsis, with GSDMD −/− mice displaying markedly enhanced survival over WT controls in models of sepsis induced by LPS and cecum ligation and puncture (CLP).…”

Section: Gasdermins and Diseasesmentioning

confidence: 99%

“…2 ). 241 , 242 As an evolutionarily conserved cell surface protein, NINJ1 facilitates cell membrane rupture and the discharge of DAMPs. 243 These DAMPs are detected by PRRs, which activates a cascade of immune responses, resulting in the attraction of immune cells and the triggering or augmentation of inflammatory reactions, which can ultimately promote the manifestation of inflammatory diseases.…”

Section: Introductionmentioning

confidence: 99%

The gasdermin family: emerging therapeutic targets in diseases

Zhu,

Xu,

Jiang

et al. 2024

Sig Transduct Target Ther

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The gasdermin (GSDM) family has garnered significant attention for its pivotal role in immunity and disease as a key player in pyroptosis. This recently characterized class of pore-forming effector proteins is pivotal in orchestrating processes such as membrane permeabilization, pyroptosis, and the follow-up inflammatory response, which are crucial self-defense mechanisms against irritants and infections. GSDMs have been implicated in a range of diseases including, but not limited to, sepsis, viral infections, and cancer, either through involvement in pyroptosis or independently of this process. The regulation of GSDM-mediated pyroptosis is gaining recognition as a promising therapeutic strategy for the treatment of various diseases. Current strategies for inhibiting GSDMD primarily involve binding to GSDMD, blocking GSDMD cleavage or inhibiting GSDMD-N-terminal (NT) oligomerization, albeit with some off-target effects. In this review, we delve into the cutting-edge understanding of the interplay between GSDMs and pyroptosis, elucidate the activation mechanisms of GSDMs, explore their associations with a range of diseases, and discuss recent advancements and potential strategies for developing GSDMD inhibitors.

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Pyroptosis-induced inflammation and tissue damage

Cited by 33 publications

References 105 publications

DAMPs and radiation injury

DAMPs and radiation injury

Crosstalk between cancer-associated fibroblasts and regulated cell death in tumors: insights into apoptosis, autophagy, ferroptosis, and pyroptosis

The gasdermin family: emerging therapeutic targets in diseases

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