Microglia and mast cells generate proinflammatory cytokines in the brain and worsen inflammatory state: Suppressor effect of IL-37

Pio Conti, Dorina Lauritano, Alessandro Caraffa, Carla Enrica Gallenga, Spiros K Kritas, Gianpaolo Ronconi, Stefano Martinotti

Risultato della ricerca: Contributo in rivistaArticolo in rivista

Abstract

Brain microglia cells are responsible for recognizing foreign bodies and act by activating other immune cells. Microglia react against infectious agents that cross the blood-brain barrier and release pro-inflammatory cytokines including interleukin (IL)-1β, IL-33 and tumor necrosis factor (TNF). Mast cells (MCs) are immune cells also found in the brain meninges, in the perivascular spaces where they create a protective barrier and release pro-inflammatory compounds, such as IL-1β, IL-33 and TNF. IL-1β binds to the IL-1R1 receptor and activates a cascade of events that leads to the production of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and activation of the immune system. IL-33 is a member of the IL-1 family expressed by several immune cells including microglia and MCs and is involved in innate and adaptive immunity. IL-33 is a pleiotropic cytokine which binds the receptor ST2 derived from TLR/IL-1R super family and is released after cellular damage (also called “alarmin”). These cytokines are responsible for a number of brain inflammatory disorders. Activated IL-1β in the brain stimulates microglia, MCs, and perivascular endothelial cells, mediating various inflammatory brain diseases. IL-37 also belongs to the IL-1 family and has the capacity to suppress IL-1β with an anti-inflammatory property. IL-37 deficiency could activate and enhance myeloid differentiation (MyD88) and p38-dependent protein-activated mitogenic kinase (MAPK) with an increase in IL-1β and IL-33 exacerbating neurological pathologies. In this article we report for the first time that microglia communicate and collaborate with MCs to produce pro-inflammatory cytokines that can be suppressed by IL-37 having a therapeutic potentiality.
Lingua originaleEnglish
pagine (da-a)N/A-N/A
RivistaEuropean Journal of Pharmacology
Volume875
DOI
Stato di pubblicazionePubblicato - 2020

Keywords

  • Cytokines
  • IL-37
  • Microglia
  • Mast cells
  • Macrophages

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