A critical role for hemolysin in Vibrio fluvialis-induced IL-1Î² secretion mediated by the NLRP3 inflammasome in macrophages

Song, Lihua; Huang, Yuanming; Zhao, Meng; Wang, Wenwen; Wang, Shujing; Sun, Hui; Kan, Biao; Meng, Guangxun; Liang, Weili; Ren, Zhihong

doi:10.3389/fmicb.2015.00510

Cited by 25 publications

(19 citation statements)

References 43 publications

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“…Mouse bone-marrow-derived macrophages (BMDMs) isolated from the wild-type (WT) C57BL/6J mice (female, eight weeks of age) and the genetically deficient mice were cultured as previously described ( 25 ). PMs were collected from peritoneal lavage according to the procedure reported by Kumagai ( 26 ).…”

Section: Methodsmentioning

confidence: 99%

Activation of the Nlrp3 Inflammasome Contributes to Shiga Toxin-Induced Hemolytic Uremic Syndrome in a Mouse Model

Song

Xiao

et al. 2021

Front. Immunol.

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ObjectiveTo explore the role of the Nlrp3 inflammasome activation in the development of hemolytic uremic syndrome (HUS) induced by Stx2 and evaluate the efficacy of small molecule Nlrp3 inhibitors in preventing the HUS.MethodsPeritoneal macrophages (PMs) isolated from wild-type (WT) C57BL/6J mice and gene knockout mice (Nlrc4-/-, Aim2-/-, and Nlrp3-/-) were treated with Stx2 in vitro and their IL-1β releases were measured. WT mice and Nlrp3-/- mice were also treated with Stx2 in vivo by injection, and the biochemical indices (serum IL-1β, creatinine [CRE] and blood urea nitrogen [BUN]), renal injury, and animal survival were compared. To evaluate the effect of the Nlrp3 inhibitors in preventing HUS, WT mice were pretreated with different Nlrp3 inhibitors (MCC950, CY-09, Oridonin) before Stx2 treatment, and their biochemical indices and survival were compared with the WT mice without inhibitor pretreatment.ResultsWhen PMs were stimulated by Stx2 in vitro, IL-1β release in Nlrp3-/- PMs was significantly lower compared to the other PMs. The Nlrp3-/- mice treated by Stx2 in vivo, showed lower levels of the biochemical indices, alleviated renal injuries, and increased survival rate. When the WT mice were pretreated with the Nlrp3 inhibitors, both the biochemical indices and survival were significantly improved compared to those without inhibitor pretreatment, with Oridonin being most potent.ConclusionNlrp3 inflammasome activation plays a vital role in the HUS development when mice are challenged by Stx2, and Oridonin is effective in preventing HUS.

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Section: Methodsmentioning

confidence: 99%

Activation of the Nlrp3 Inflammasome Contributes to Shiga Toxin-Induced Hemolytic Uremic Syndrome in a Mouse Model

Song

Xiao

et al. 2021

Front. Immunol.

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“…To confirm the percentage of M2 macrophages in the IL-4- stimulated RAW264.7 cells, we analyzed the positive rate of CD206, a widely utilized surface marker of M2 macrophages, 16 by flow cytometry. Corresponding fluorescence label-conjugated isotype controls were utilized in this experiment.…”

Section: Methodsmentioning

confidence: 99%

Characteristics and potential role of M2 macrophages in COPD

He¹,

Xie²,

Lu³

et al. 2017

COPD

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BackgroundCOPD is a multi-pathogenesis disease mainly caused by smoking. A further understanding of the mechanism of smoking-related COPD might contribute to preventions and treatments of this disease in the early stages. This study was designed to identify the characteristics of M2 macrophages in COPD for a better understanding about their potential role.Materials and methodsCOPD models were built in the C57BL/6 mouse by cigarette smoke (CS) exposure combined with intraperitoneal injection of cigarette smoke extract (CSE). The modeling efficiency was evaluated by lung function and hematoxylin and eosin (H&E) staining. The number of different macrophage phenotypes was detected by immunohistochemical staining (IHS) of CD206, CD86 and CD68 on the lung tissue paraffin section. The RAW264.7 cells were polarized toward the M2 phenotype by interleukin IL-4 and confirmed by a flow cytometer. The gene expression levels of TGF-βRII, Smad2, Smad3 and Smad7 in CSE-treated M2 macrophages were detected by real-time reverse transcription polymerase chain reaction (RT-PCR). The expression levels of TGF-β/Smad pathway-related makers (TGF-βRII, p-Smad2, p-Smad3, Smad7 and TGF-β) in alveolar M2 macrophages were detected by two consecutive paraffin section IHS.ResultsThe COPD model is well established, which is confirmed by the lung function test and lung H&E staining. The whole number of macrophages and the ratio of M2/M1 phenotype are both increased (p<0.05). The level of CD206+ cells in IL-4-stimulated RAW264.7 cells is up to 93.4%, which is confirmed by a flow cytometer. The gene expression of TGF-βRII, Smad2, Smad3 and Smad7 are all enhanced (p<0.05) in CES-treated M2 macrophages, which is detected by RT-PCR. The protein levels of TGF-β/Smad pathway-related markers are all increased in alveolar M2 macrophages of the model group.ConclusionThis study found an increased deposition of alveolar M2 macrophages in the mouse COPD model and an increased expression level of TGF-β/Smad pathway in M2 macrophages, both in vitro and in vivo, induced by CSE and/or CS exposure, indicating that M2 macrophages might contribute to COPD through changing of phenotype and TGF-β/Smad pathway.

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“…Mouse bone-marrow-derived macrophages (BMDMs) were isolated from the abovementioned mice and cultured as previously described (Song et al, 2015). Peritoneal macrophages (PMs) were collected from peritoneal lavage using the procedure utilized by Kumagai et al (1979).…”

Section: Mice and Cell Culturementioning

confidence: 99%

Contribution of Nlrp3 Inflammasome Activation Mediated by Suilysin to Streptococcal Toxic Shock-like Syndrome

Song¹,

Xiao

et al. 2020

Front. Microbiol.

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The aim of this study was to investigate the molecular mechanism of inflammasome activation in response to Streptococcus suis serotype 2 (SS2) infection and its contribution to the development of streptococcal toxic shock-like syndrome (STSS). Methods: To verify the role of suilysin (SLY) in STSS, we infected bone-marrow-derived macrophages (BMDMs) in vitro and C57BL/6J mice intraperitoneally (IP) with the SS2 wild-type (WT) strain or isogenic sly mutant (∆SLY) to measure the interleukin (IL)-1β release and survival rate. To determine the role of inflammasome activation and pyroptosis in STSS, we infected BMDMs from WT and various deficient mice, including Nlrp3-deficient (Nlrp3 −/−), Nlrc4-deficient (Nlrc4 −/−), Asc-deficient (Asc −/−), Aim2-deficient (Aim2 −/−), Caspase-1/11-deficient (Caspase-1/11 −/−), and Gsdmd-deficient (Gsdmd −/−) ex vivo, and IP injected WT, Nlrp3 −/− , Caspase-1/11 −/− , and Gsdmd −/− mice with SS2, to compare the IL-1β releases and survival rate in vivo. Results: The SS2-induced IL-1β production in mouse macrophages is mediated by SLY ex vivo. The survival rate of WT mice infected with SS2 was significantly lower than that of mice infected with the ∆SLY strain in vivo. Furthermore, SS2-triggered IL-1β releases, and the cytotoxicity in the BMDMs required the activation of the NOD-Like Receptors Family Pyrin Domain Containing 3 (Nlrp3), Caspase-1/11, and gasdermin D (Gsdmd) inflammasomes, but not the Nlrc4 and Aim2 inflammasomes ex vivo. The IL-1β production and survival rate of WT mice infected with SS2 were significantly lower than those of the Nlrp3 −/− , Caspase-1/11 −/− , and Gsdmd −/− mice in vivo. Finally, the inhibitor of the Nlrp3 inflammasome could reduce the IL-1β release and cytotoxicity of SS2-infected macrophages ex vivo and protect SS2-infected mice from death in vivo. Conclusion: Nlrp3 inflammasome activation triggered by SLY in macrophages played an important role in the pathogenesis of STSS.

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A critical role for hemolysin in Vibrio fluvialis-induced IL-1Î² secretion mediated by the NLRP3 inflammasome in macrophages

Cited by 25 publications

References 43 publications

Activation of the Nlrp3 Inflammasome Contributes to Shiga Toxin-Induced Hemolytic Uremic Syndrome in a Mouse Model

Activation of the Nlrp3 Inflammasome Contributes to Shiga Toxin-Induced Hemolytic Uremic Syndrome in a Mouse Model

Characteristics and potential role of M2 macrophages in COPD

Contribution of Nlrp3 Inflammasome Activation Mediated by Suilysin to Streptococcal Toxic Shock-like Syndrome

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