Cell Volume Regulation Modulates NLRP3 Inflammasome Activation

Compan, Vincent; Baroja‐Mazo, Alberto; López-Castejón, Gloria; Gómez, Ana Isabel Sanz; Martínez, Carlos; Angosto-Bazarra, Diego; Montero, M. Teresa; Herranz, Arantxa; Bazán, Eulalia; Reimers, Diana; Mulero, Víctoriano; Pelegrı́n, Pablo

doi:10.1016/j.immuni.2012.06.013

Cited by 338 publications

(351 citation statements)

References 54 publications

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“…Cells possess different volume sensor systems, such as the calcium-permeable channel protein TRP, driving RVD in macrophages. The activation of these channels and the associated ionic changes activate TAK1, a MAPKK kinase, necessary for hypotonicity-, alum-, ATP-and nigericin-induced mature IL-1␤ release and inflammation (7,8). In this study, we confirmed the implication of TRP in IL-1␤ release by macrophages in response to hypotonic shock.…”

Section: Discussionmentioning

confidence: 99%

“…In this case, TRP activation required AQP (31). The RVD process implies an efflux of intracellular K ϩ that has been shown to be necessary for inflammasome activation in response to various stimuli, including hypotonic shock (5,7,20). In this study, we found that intracellular potassium decrease was not reduced by AQP1 deficiency in lung macrophages exposed to hypotonic shock (data not shown).…”

Section: Discussionmentioning

confidence: 99%

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Critical Role of Aquaporins in Interleukin 1β (IL-1β)-induced Inflammation

Rabolli

Wallemme

et al. 2014

Journal of Biological Chemistry

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Background: Aquaporins are channels permeable to water, and they are essential for immune cell migration. Results: We demonstrate that aquaporin-mediated water fluxes are necessary for the NLRP3 inflammasome-dependent release of mature IL-1␤ in vitro and in vivo. Conclusion: Aquaporins are implicated in the mechanisms of proinflammatory cytokine secretion during inflammation. Significance: The discovery of a new function for AQPs opens new diagnostic and therapeutic opportunities in inflammatory disorders.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Critical Role of Aquaporins in Interleukin 1β (IL-1β)-induced Inflammation

Rabolli

Wallemme

et al. 2014

Journal of Biological Chemistry

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“…Then, a second stimulus (e.g., pore-forming toxins, bacterial invasion, or uptake of large particulates) induces the formation of the NLRP3 inflammasome (4). Although NLRP3 "ligands" are highly diverse, they all seem to converse in the efflux of K + from the cell, which is proposed to be the common trigger (11,12).…”

mentioning

confidence: 99%

Inflammasome Activation by Campylobacter jejuni

Bouwman¹,

Zoete²,

Bleumink-Pluym³

et al. 2014

The Journal of Immunology

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The Gram-negative pathogen Campylobacter jejuni is the most common cause of bacterial foodborne disease worldwide. The mechanisms that lead to bacterial invasion of eukaryotic cells and massive intestinal inflammation are still unknown. In this study, we report that C. jejuni infection of mouse macrophages induces upregulation of pro–IL-1β transcript and secretion of IL-1β without eliciting cell death. Immunoblotting indicated cleavage of caspase-1 and IL-1β in infected cells. In bone marrow–derived macrophages from different knockout mice, IL-1β secretion was found to require NLRP3, ASC, and caspase-1/11 but not NLRC4. In contrast to NLRP3 activation by ATP, C. jejuni activation did not require priming of these macrophages. C. jejuni also activated the NLRP3 inflammasome in human macrophages as indicated by the presence of ASC foci and caspase-1–positive cells. Analysis of a vast array of C. jejuni mutants with defects in capsule formation, LPS biosynthesis, chemotaxis, flagella synthesis and flagellin (-like) secretion, type 6 secretion system needle protein, or cytolethal distending toxin revealed a direct correlation between the number of intracellular bacteria and NLRP3 inflammasome activation. The C. jejuni invasion–related activation of the NLRP3 inflammasome without cytotoxicity and even in nonprimed cells extends the known repertoire of bacterial inflammasome activation and likely contributes to C. jejuni–induced intestinal inflammation.

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“…Colocalization of NLRP3 and NLRC4 was only partial, with NLRP3 composing a ring with lower diameter than NLRC4 [64]. Interestingly, while hypoosmotic conditions activate the NLRP3 inflammasome due to K + efflux and Ca 2+ influx [65], hyperosmotic conditions signal through NLRP3 and NLRC4, independently of K + efflux (Fig. 5).…”

Section: The Role Of Asc In Cytokine Maturation and Pyroptosismentioning

confidence: 95%

The NLRC4 inflammasome: The pieces of the puzzle are falling into place

Hafner-Bratkovič¹

2017

Inflammasome

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Inflammasomes are intracellular multiprotein platforms for the activation of inflammatory caspases. As components of the innate immune system, they play an important role in the fight against microbes. However, aberrant inflammasome activation has been implicated in auto-inflammatory syndromes. This review focuses on the NLRC4 inflammasome. This is perhaps not the most extensively studied, yet its mechanism of activation is by far the best understood. The NLRC4 inflammasome is activated by several proteins originating from intracellular bacteria, which are first sensed by receptors of the NAIP family. Activated NAIP binds NLRC4, which further recruits dormant NLRC4 molecules in a prion-like oligomerization event. NLRC4 enables a strong amplification of the signal, providing a fast and robust host response. The review also discusses peculiar NLRC4 inflammasome functions in promoting eicosanoid biosynthesis, actin reorganization, and its roles in autoinflammatory syndromes and sterile inflammation. Finally, the first inflammasomeindependent engagement of NLRC4 in suppressing melanoma tumor growth is presented. The emerging roles of NLRC4 in various normal and pathological processes demonstrate that there is still plenty to be learned about the NLRC4 mechanism of activation and downstream functions.

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Cell Volume Regulation Modulates NLRP3 Inflammasome Activation

Cited by 338 publications

References 54 publications

Critical Role of Aquaporins in Interleukin 1β (IL-1β)-induced Inflammation

Critical Role of Aquaporins in Interleukin 1β (IL-1β)-induced Inflammation

Inflammasome Activation by Campylobacter jejuni

The NLRC4 inflammasome: The pieces of the puzzle are falling into place

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