P2X7R activation drives distinct IL-1 responses in dendritic cells compared to macrophages

Englezou, Pavlos C.; Rothwell, Simon; Ainscough, Joseph S.; Brough, David; Landsiedel, Robert; Verkhratsky, Alexei; Kimber, Ian; Dearman, Rebecca J.

doi:10.1016/j.cyto.2015.05.013

Cited by 28 publications

(20 citation statements)

References 48 publications

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“…Alongside surface recognition by TLR2, strain 89-1591-induced IL-1β production was partially internalization-dependent, with residual levels of IL-1β being similar to those induced by lipopolysaccharide (which does not activate inflammasome assembly) when blocking internalization [53,54]. A similar internalization-dependent mechanism of IL-1β production was previously described for Streptococcus pneumoniae [55].…”

Section: Discussionsupporting

confidence: 64%

Recognition of Lipoproteins by Toll-like Receptor 2 and DNA by the AIM2 Inflammasome Is Responsible for Production of Interleukin-1β by Virulent Suilysin-Negative Streptococcus suis Serotype 2

et al. 2020

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Streptococcus suis serotype 2 is an important porcine bacterial pathogen and zoonotic agent causing sudden death, septic shock and meningitis. These pathologies are the consequence of an exacerbated inflammatory response composed of various mediators including interleukin (IL)-1β. Elevated levels of the toxin suilysin (SLY) were demonstrated to play a key role in S. suis-induced IL-1β production. However, 95% of serotype 2 strains isolated from diseased pigs in North America, many of which are virulent, do not produce SLY. In this study, we demonstrated that SLY-negative S. suis induces elevated levels of IL-1β in systemic organs, with dendritic cells contributing to this production. SLY-negative S. suis-induced IL-1β production requires MyD88 and TLR2 following recognition of lipoproteins. However, the higher internalization rate of the SLY-negative strain results in intracellularly located DNA being recognized by the AIM2 inflammasome, which promotes IL-1β production. Finally, the role of IL-1 in host survival during the S. suis systemic infection is beneficial and conserved, regardless of SLY production, via modulation of the inflammation required to control bacterial burden. In conclusion, this study demonstrates that SLY is not required for S. suis-induced IL-1β production.

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Section: Discussionsupporting

confidence: 64%

Recognition of Lipoproteins by Toll-like Receptor 2 and DNA by the AIM2 Inflammasome Is Responsible for Production of Interleukin-1β by Virulent Suilysin-Negative Streptococcus suis Serotype 2

et al. 2020

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“…Activation of P2X7 causes IL-1b maturation and release from antigen-presenting cells [29], a proinflammatory cytokine implicated in the pathogenesis of GVHD [30]. Moreover, P2X7-mediated IL-1b release is involved in the production of IFN-g [31] and IL-17 [32].…”

Section: Bbg Does Not Alter Murine or Human Il-1b Expression In Humanmentioning

confidence: 99%

The P2X7 receptor antagonist Brilliant Blue G reduces serum human interferon-γ in a humanized mouse model of graft-versus-host disease

Geraghty

Belfiore

et al. 2017

Clinical and Experimental Immunology

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Graft-versus-host disease (GVHD) remains a major problem after allogeneic haematopoietic stem cell transplantation, a curative therapy for haematological malignancies. Previous studies have demonstrated a role for the adenosine triphosphate (ATP)-gated P2X7 receptor channel in allogeneic mouse models of GVHD. In this study, injection of human peripheral blood mononuclear cells (PBMCs) into immunodeficient non-obese diabetic-severe combined immunodeficiency-interleukin (NOD-SCID-IL)-2Rγ (NSG) mice established a humanized mouse model of GVHD. This model was used to study the effect of P2X7 blockade in this disease. From five weeks post-PBMC injection, humanized mice exhibited clinical signs and histopathology characteristic of GVHD. The P2X7 antagonist, Brilliant Blue G (BBG), blocked ATP-induced cation uptake into both murine and human cells in vitro. Injection of BBG (50 mg/kg) into NSG mice did not affect engraftment of human leucocytes (predominantly T cells), or the clinical score and survival of mice. In contrast, BBG injection reduced circulating human interferon (IFN)-γ significantly, which was produced by human CD4 and CD8 T cells. BBG also reduced human T cell infiltration and apoptosis in target organs of GVHD. In conclusion, the P2X7 antagonist BBG reduced circulating IFN-γ in a humanized mouse model of GVHD supporting a potential role for P2X7 to alter the pathology of this disease in humans.

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“…CHANG-MIN LEE 1* , DAE-SUNG LEE 2* , WON-KYO JUNG 3* , JONG SU YOO 2 , MI-JIN YIM 2 , YUNG HYUN CHOI 4 , SAEGWANG PARK 5 , SU-KIL SEO 5 , JUNG SIK CHOI 6 , YOUNG-MIN LEE 6 , WON SUN PARK 7 and IL-WHAN CHOI 5 by an inflammasome assembly with NLRP3, ASC and procaspase-1. LPS must induce IL-1β for caspase-1 activation in response to adenosine triphosphate (ATP), which is a well-characterized danger-associated molecular pattern (DAMP) (9,10). Extracellular ATP promotes NLRP3 inflammasome activation by stimulating purinergic receptor P2X ligand-gated ion channel 7 (P2X7) (11,12).…”

Section: Benzyl Isothiocyanate Inhibits Inflammasome Activation In Ementioning

confidence: 99%

Benzyl isothiocyanate inhibits inflammasome activation in E. coli LPS-stimulated BV2 cells

Lee

Jung

et al. 2016

International Journal of Molecular Medicine

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Inflammasomes are multi-protein complexes that play a crucial role in innate immune responses. Benzyl isothiocyanate (BITC) is a naturally occurring compound found in cruciferous vegetables, and BITC exhibits potential as a chemopreventive agent. However, whether BITC exerts inflammasome-mediated regulatory effects on neuroinflammation is unknown. In this study, we examined the effects of BITC on inflammasome-mediated interleukin-1β (IL-1β) production in E. coli lipopolysaccharide (LPS)-stimulated BV2 microglial cells. IL-1β production is tightly regulated at the post-translational level through the inflammasoume. We measured the levels of IL-1β produced from the LPS-exposed BV2 microglial cells using enzyme-linked immunosorbent assays (ELISAs). The BITC regulatory mechanisms in inflammasome-mediated cellular signaling pathways were examined by RT-PCR, western blot analysis and electrophoretic mobility shift assays. BITC inhibited the secretion of IL-1β induced by LPS in the BV2 microglial cells. BITC inhibited inflammasome activation and NLR family, pyrin domain containing 3 (NLRP3)-mediated caspase-1 activation, and decreased the levels of inflammasome activation pro-inflammatory mediators, including mitochondrial reactive oxygen species (ROS) and adenosine triphosphate (ATP) secretion in the LPS-stimulated BV2 microglial cells. Furthermore, we demonstrated that nuclear factor-κB (NF-κB) activation induced by LPS was inhibited by BITC, which may contribute to the attenuated secretion of IL-1β. These BITC-mediated inhibitory effects on IL-1β expression may thus regulate neuroinflammation through the inflammasome-mediated signaling pathway.

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P2X7R activation drives distinct IL-1 responses in dendritic cells compared to macrophages

Abstract: HighlightsP2X7R-driven IL-1 responses are markedly enhanced in BMDC compared to BMM.P2X7R antagonist A-740003 inhibitedIL-1 release in BMDC and BMM.P2X7R-induced pore formation was greater in BMDC than in BMM.LPS-primed BMDC resisted ATP-induced cell death in comparison to BMM.

Cited by 28 publications

References 48 publications

Recognition of Lipoproteins by Toll-like Receptor 2 and DNA by the AIM2 Inflammasome Is Responsible for Production of Interleukin-1β by Virulent Suilysin-Negative Streptococcus suis Serotype 2

Recognition of Lipoproteins by Toll-like Receptor 2 and DNA by the AIM2 Inflammasome Is Responsible for Production of Interleukin-1β by Virulent Suilysin-Negative Streptococcus suis Serotype 2

The P2X7 receptor antagonist Brilliant Blue G reduces serum human interferon-γ in a humanized mouse model of graft-versus-host disease

Benzyl isothiocyanate inhibits inflammasome activation in E. coli LPS-stimulated BV2 cells

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