The unconventional secretion of IL-1β: Handling a dangerous weapon to optimize inflammatory responses

Sitia, Roberto; Rubartelli, Anna

doi:10.1016/j.semcdb.2018.03.011

Cited by 51 publications

(41 citation statements)

References 96 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This further activates Caspase-1, which, in this case, does not act as an apoptosis stimulus but rather converts cytokines such as IL-1β and IL-18 from their inactive into their active form. This mechanism could account for the observation that IL-1β release was only detected in monocytes after treatment with metal salts as the activation of IL-1β secretion requires a "second signal" [34]. However, THP-1 macrophages already showed a high basic IL-1β release in the untreated cells, which was not influenced by metal ion treatment.…”

Section: Discussionmentioning

confidence: 89%

Comparison of Inflammatory Effects in THP-1 Monocytes and Macrophages after Exposure to Metal Ions

et al. 2020

View full text Add to dashboard Cite

Monocytes and macrophages are the first barrier of the innate immune system, which interact with abrasion and corrosion products, leading to the release of proinflammatory mediators and free reactive molecules. The aim of this study was to understand inflammation-relevant changes in monocytes and macrophages after exposure to corrosion products. To do this, the THP-1 cell line was used to analyze the effects of metal ions simultaneously in monocytes and differentiated macrophages. Cells were stimulated with several concentrations of metal salts (CoCl2, NiCl2, CrCl3 × 6H2O) to analyze viability, gene expression, protein release and ROS production. Untreated cells served as negative controls. While exposure to Cr(3+) did not influence cell viability in both cell types, the highest concentration (500 µM) of Co(2+) and Ni(2+) showed cytotoxic effects mirrored by significantly reduced metabolism, cell number and a concomitant increase of ROS. The release of IL-1β, IL-8, MCP-1 and M-CSF proteins was mainly affected in macrophages after metal ion exposure (100 µM), indicating a higher impact on pro-inflammatory activity. Our results prove that monocytes and macrophages react very sensitively to corrosion products. High concentrations of bivalent ions lead to cell death, while lower concentrations trigger the release of inflammatory mediators, mainly in macrophages.

show abstract

Section: Discussionmentioning

confidence: 89%

Comparison of Inflammatory Effects in THP-1 Monocytes and Macrophages after Exposure to Metal Ions

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Several mechanisms have been suggested (reviewed in refs. [38][39][40], including: (1) accumulation of IL-1β within membrane-bound subcellular compartments (exosomes, microvesicles, secretory lysosomes) for export to the extracellular space in the absence of lysis; (2) prelytic efflux of IL-1β via active plasma membrane GSDMD pores; and (3) IL-1β release as a passive consequence of GSDMDdependent pyroptosis. It is unclear whether the membrane compartmentalization pathways operate independently of GSDMD, or whether they are regulated (directly or indirectly) by GSDMD.…”

Section: Macrophagementioning

confidence: 99%

N-GSDMD trafficking to neutrophil organelles facilitates IL-1β release independently of plasma membrane pores and pyroptosis

et al. 2020

View full text Add to dashboard Cite

Gasdermin-D (GSDMD) in inflammasome-activated macrophages is cleaved by caspase-1 to generate N-GSDMD fragments. N-GSDMD then oligomerizes in the plasma membrane (PM) to form pores that increase membrane permeability, leading to pyroptosis and IL-1β release. In contrast, we report that although N-GSDMD is required for IL-1β secretion in NLRP3activated human and murine neutrophils, N-GSDMD does not localize to the PM or increase PM permeability or pyroptosis. Instead, biochemical and microscopy studies reveal that N-GSDMD in neutrophils predominantly associates with azurophilic granules and LC3 + autophagosomes. N-GSDMD trafficking to azurophilic granules causes leakage of neutrophil elastase into the cytosol, resulting in secondary cleavage of GSDMD to an alternatively cleaved N-GSDMD product. Genetic analyses using ATG7-deficient cells indicate that neutrophils secrete IL-1β via an autophagy-dependent mechanism. These findings reveal fundamental differences in GSDMD trafficking between neutrophils and macrophages that underlie neutrophil-specific functions during inflammasome activation.

show abstract

“…Moreover, another critical nding of our study was that miR-214 overexpression could downregulate the expression of IL-1β, TNF-and IL-6 and repress pulmonary angiogenesis and alveolarization in hyperoxiainduced BPD neonatal rats. IL-1β is one of the main mediators of in ammation and plays a causative role in innumerable diseases [30]. In the primary pathological features of BPD, IL-1β contributes to excessive alveolar elastogenesis through the interaction with αvβ6 which serves as an epithelial or a mesenchymal signaling molecule [31].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-214 Prevents Pulmonary Angiogenesis and Alveolarization in Rat Models with Bronchopulmonary Dysplasia via PlGF-Dependent STAT3 Signaling Pathway

Zhiqun

Hong

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: In recent years, the roles of microRNAs (miRNAs) in pulmonary diseases have been widely studied and researched. However, the molecular mechanism by which miR-214 affects bronchopulmonary dysplasia (BPD) remains elusive and merits further exploration. Hence, this study aims to clarify the function of miR-214 in pulmonary angiogenesis and alveolarization in preterm infants with BPD. Methods: BPD neonatal rat model was induced by hyperoxia, and pulmonary epithelial cells were isolated from rats and exposed to hyperoxia. Gain- or loss-of-function experiments were performed in BPD neonatal rats and hyperoxic pulmonary epithelial cells. MiR-214 and PlGF expression in BPD neonatal rats, and eNOS, Bcl-2, c-myc, Survivin, α-SMA and E-cadherin expression in hyperoxic pulmonary epithelial cells were detected using RT-qPCR and western blot analysis. The interaction between PlGF and miR-214 was identified using dual luciferase reporter gene assay and RIP assay. ELISA was adopted to assess IL-1β, TNF-a, IL-6, ICAM-1 and Flt-1 expression in rats. Results: Decreased miR-214 expression and elevated PlGF expression were evident in the lung tissues of neonatal rats with BPD. PlGF was a target of miR-214, and miR-214 downregulated PlGF to inactivate the STAT3 signaling pathway. miR-214 overexpression or PlGF silencing decreased apoptosis of hyperoxic pulmonary epithelial cells and declined pulmonary angiogenesis and alveolarization in BPD neonatal rats. Conclusions: Collectively, miR-214 can protects against pulmonary angiogenesis and alveolarization in preterm infants with BPD by suppressing PlGF and blocking STAT3 signaling pathway.

show abstract

The unconventional secretion of IL-1β: Handling a dangerous weapon to optimize inflammatory responses

Cited by 51 publications

References 96 publications

Comparison of Inflammatory Effects in THP-1 Monocytes and Macrophages after Exposure to Metal Ions

Comparison of Inflammatory Effects in THP-1 Monocytes and Macrophages after Exposure to Metal Ions

N-GSDMD trafficking to neutrophil organelles facilitates IL-1β release independently of plasma membrane pores and pyroptosis

MicroRNA-214 Prevents Pulmonary Angiogenesis and Alveolarization in Rat Models with Bronchopulmonary Dysplasia via PlGF-Dependent STAT3 Signaling Pathway

Contact Info

Product

Resources

About