IRGM restrains NLRP3 inflammasome activation by mediating its SQSTM1/p62-dependent selective autophagy

Mehto, Subhash; Chauhan, Swati; Jena, Kautilya Kumar; Nath, Parej; Sahu, Rinku; Dhar, Kollori; Das, Saroj Kumar; Chauhan, Santosh

doi:10.1080/15548627.2019.1628544

Cited by 35 publications

(34 citation statements)

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“…Because it has been demonstrated that autophagy has important effects on the induction of the inflammatory reaction, 6 , 24 we investigated the relationship between Sal-miR-58-induced autophagy and inflammation in Ang II-treated VSMCs. Western blot analysis showed that treating VSMCs with Ang II clearly reduced the expression of Beclin1 and Atg5, which was reversed by Sal-miR-58 transfection, as evidenced by increased expression of Beclin1 and Atg5 as well as by enhanced conversion of LC3BI to LC3BII ( Figure 3 A).…”

Section: Resultsmentioning

confidence: 99%

Salvia miltiorrhiza-Derived Sal-miR-58 Induces Autophagy and Attenuates Inflammation in Vascular Smooth Muscle Cells

Qin

Zheng

Yang

et al. 2020

Molecular Therapy - Nucleic Acids

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Section: Resultsmentioning

confidence: 99%

Salvia miltiorrhiza-Derived Sal-miR-58 Induces Autophagy and Attenuates Inflammation in Vascular Smooth Muscle Cells

Qin

Zheng

Yang

et al. 2020

Molecular Therapy - Nucleic Acids

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“…Recent studies have demonstrated that IRGM is a key negative regulator of NLRP3 inflammasome activation by interacting with NLRP3 and ASC and subsequently inhibiting inflammasome assembly [71]. In line with this, IRGM mediates the autophagic degradation of NLRP3 components [72]. However, there is still relatively less known regarding the function of IRGM in cancer.…”

Section: Autophagy-related Moleculesmentioning

confidence: 95%

Crosstalks between inflammasome and autophagy in cancer

et al. 2020

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Both inflammasomes and autophagy have important roles in the intracellular homeostasis, inflammation, and pathology; the dysregulation of these processes is often associated with the pathogenesis of numerous cancers. In addition, they can crosstalk with each other in multifaceted ways to influence various physiological and pathological responses, including cancer. Multiple molecular mechanisms connect the autophagy pathway to inflammasome activation and, through this, may influence the outcome of pro-tumor or anti-tumor responses depending on the cancer types, microenvironment, and the disease stage. In this review, we highlight the rapidly growing literature on the various mechanisms by which autophagy interacts with the inflammasome pathway, to encourage additional applications in the context of tumors. In addition, we provide insight into the mechanisms by which pathogen modulates the autophagy-inflammasome pathway to favor the infection-induced carcinogenesis. We also explore the challenges and opportunities of using multiple small molecules/agents to target the autophagy/inflammasome axis and their effects upon cancer treatment. Finally, we discuss the emerging clinical efforts assessing the potential usefulness of targeting approaches for either autophagy or inflammasome as anticancer strategies, although it remains underexplored in terms of their crosstalks.

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“…Previous studies have shown that autophagy regulates the activation of microglia and in ammatory response [69][70][71]. The activation of NLRP3 in ammasome is inhibited by autophagy through the clearance of damaged mitochondria degradation of the NLRP3 in ammasome [42,72,73]. Therefore, we used western blot analysis to detect the expression of NLRP3 and related in ammatory factors, IL-18 and IL-1β.…”

Section: Autophagy Induction Attenuated the Ntg-evoked Activation Of mentioning

confidence: 99%

P2X7R-mediated Autophagic Impairment Contributes to Central Sensitization in a chronic Migraine Model with Recurrent Nitroglycerin Stimulation in Mice

Jiang

Zhang

Feng

et al. 2020

Preprint

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Background: Central sensitization is an important pathophysiological mechanism of chronic migraine (CM). According to our previous studies, microglial activation and subsequent inflammation in the trigeminal nucleus caudalis (TNC) contribute to the central sensitization. The P2X7 receptor (P2X7R) is a purinergic receptor expressed in microglia and participates in central sensitization in chronic pain, but its role in CM is unclear. Numerous studies have shown that P2X7R regulates the level of autophagy and that autophagy affects the microglial activation and inflammation. Recently, autophagy has been shown to be involved in neuropathic pain, but there is no information about autophagy in CM. Therefore, the current study investigated the role of P2X7R in CM and its underlying mechanism, focusing on autophagy regulation.Methods: The CM model was established by repeated intraperitoneal injection of nitroglycerin (NTG) in mice. A Von Frey filament and radiant heat were used to assess the mechanical and thermal hypersensitivity. Western blotting and immunofluorescence assays were performed to detect the expression of P2X7R, autophagy-related proteins, and the cellular localization of P2X7R. To determine the role of P2X7R and autophagy in CM, we detected the effects of the autophagy inducer, rapamycin (RAPA) and P2X7R antagonist, Brilliant Blue G (BBG), on pain behavior and the expression of calcitonin gene-related peptide (CGRP) and c-fos. In addition, the effect of RAPA and BBG on microglial activation and subsequent inflammation were investigated.Results: The expression of P2X7R was increased and was mainly colocalized with microglia in the TNC following recurrent NTG administration. The autophagic flux was blocked in CM, which was characterized by up-regulated LC3-II, and accumulated autophagy substrate protein, p62. RAPA significantly improved the basal rather than acute hyperalgesia. BBG alleviated both basal and acute hyperalgesia. BBG activated the level of autophagic flux. RAPA and BBG inhibited the activation of microglia, limited the inflammatory response, and reduced the expression of CGRP and c-fos. Conclusions: Our results demonstrate the dysfunction of the autophagic process in CM. Activated autophagy may have a preventive effect on migraine chronification. P2X7R contributes to central sensitization through mediating autophagy regulation and might become a potential target for CM.

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IRGM restrains NLRP3 inflammasome activation by mediating its SQSTM1/p62-dependent selective autophagy

Cited by 35 publications

References 1 publication

Salvia miltiorrhiza-Derived Sal-miR-58 Induces Autophagy and Attenuates Inflammation in Vascular Smooth Muscle Cells

Salvia miltiorrhiza-Derived Sal-miR-58 Induces Autophagy and Attenuates Inflammation in Vascular Smooth Muscle Cells

Crosstalks between inflammasome and autophagy in cancer

P2X7R-mediated Autophagic Impairment Contributes to Central Sensitization in a chronic Migraine Model with Recurrent Nitroglycerin Stimulation in Mice

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