bims-stacyt Biomed News
on Metabolism and the paracrine crosstalk between cancer and the organism
Issue of 2018–09–09
two papers selected by
Cristina Muñoz Pinedo, L’Institut d’Investigació Biomèdica de Bellvitge
  1. Loss of sterol metabolic homeostasis triggers inflammasomes - how and why.
  2. Apoptosis signal-regulating kinase 1 silencing on astroglial inflammasomes in an experimental model of ischemic stroke.
  1. Curr Opin Immunol. 2018 Aug 29. pii: S0952-7915(18)30073-6. [Epub ahead of print]56 1-9
    Loss of sterol metabolic homeostasis triggers inflammasomes - how and why.
    Eric V Dang, Jason G Cyster.
      Proper regulation of sterol biosynthesis is critical for eukaryotic cellular homeostasis. Cholesterol and isoprenoids serve key roles in eukaryotic cells by regulating membrane fluidity and correct localization of proteins. It is becoming increasingly appreciated that dysregulated sterol metabolism engages pathways that lead to inflammation. Of particular importance are inflammasomes, which are multiplatform protein complexes that activate caspase-1 in order to process the pro-inflammatory and pyrogenic cytokines IL-1β and IL-18. In this review, we highlight recent research that links altered sterol biosynthetic pathway activity to inflammasome activation. We discuss how clues from human genetics have led to new insights into how alterations in isoprenoid biosynthesis connect to inflammation. We also discuss new mechanisms that show how macrophage cholesterol buildup can lead to inflammasome activation.
    DOI:  https://doi.org/10.1016/j.coi.2018.08.001
  2. Neuroscience. 2018 Aug 30. pii: S0306-4522(18)30565-7. [Epub ahead of print]
    Apoptosis signal-regulating kinase 1 silencing on astroglial inflammasomes in an experimental model of ischemic stroke.
    So Yeong Cheon, Eun Jung Kim, So Yeon Kim, Jeong Min Kim, Eun Hee Kam, Jong-Kwang Park, Bon-Nyeo Koo.
      Activation of the inflammasome complex contributes to the inflammatory response and cell death under pathologic conditions. The nucleotide binding oligomerization domain-like receptor pyrin domain-containing 2 (NLRP2) inflammasome is activated in astrocytes after cerebral ischemia, which can aggravate ischemic damage. Apoptosis signal-regulating kinase 1 (ASK1) is an early activator and immune-regulator after ischemic injury, that can lead to cell death. The objective of the present study was to evaluate the role of ASK1 in controlling NLRP2 inflammasomes in astrocytes after cerebral ischemia. In a mouse model of ischemic stroke, the levels of NLRP2 inflammasome components, and interleukin (IL)-1β and IL-18, were quantified in different brain regions. In addition, an astrocyte cell line was subjected to oxygen-glucose deprivation and reperfusion (OGD/R) injury, and the levels of NLRP2 inflammasome factors, IL-1β and IL-18 were evaluated. Ischemic brain injury activated astrocytes. The levels of NLRP2 inflammasome components, IL-1β and IL-18 productions, and cell death increased in the cortex and striatum after ischemic injury. In cultured astrocytes, NLRP2 inflammasome components, IL-1β and IL-18 levels were upregulated after OGD/R. ASK1 silencing or inhibition efficiently reduced NLRP2 inflammasome components and pro-inflammatory cytokine levels in mice and cultured astrocytes. Our findings identify a key role for ASK1 in regulating astroglial inflammasomes after cerebral ischemia. We suggest ASK1 as one of the main targets for astroglial inflammasomes in ischemic stroke.
    Keywords:  Apoptosis signal-regulating kinase 1; Astrocyte; Inflammasomes; Inflammatory response; Ischemic stroke
    DOI:  https://doi.org/10.1016/j.neuroscience.2018.08.020
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