Role of inflammasome signaling in development and function of mast cells

Esmaeil Mortaz, Gert Folkerts, Aletta Kraneveld, Mirjam Kool, Bart Lambrecht, Johan Garssen, Frank Redegeld

Research output: Contribution to conferenceAbstractOther research output

Abstract

The inflammasome is a cytosolic molecular complex containing a ASC,caspase1 and NALP that mediate the maturation of the proinflammatory cytokines IL-1β by caspases-1. NALP3 is an intracellular receptor involved in the recognition of pathogen associated molecular patterns (PAMPs).The inflammasome signal transduction promotes the maturation of inflammatory cytokines 1L-1β.The levels of 1L-1β has been shown increased in lung disease like asthma and emphysema.Mast cells(MC)play as effector cells for IgE mediated allergic diseases.Besides, recent evidence indicates that MCs also function as important cells in immune surveillance. Not much is known about role of inflammasomes in biology and development of mast cells.In this study we investigated the role of NALP3/ASC in mast cells.Development and function of mast cells, derived from a culture of bone marrow cells of wild-type, ASC-/-, NALP3-/-mice was studied. Bone marrow cells were cultured in presence for 3 weeks. After 3 weeks the responsiveness of mast cells to IgE/Ag and LPS was studied.Results:We found that in ASC-/-,NALP3-/- mast cells,the cellular maturation and differentiation was decreased as evidenced by a lower expression of c-kit and Fc{epsilon}RI. Degranulation and the production of TNF-α,IL-6 and IL-1β after stimulation by IgE/Ag or LPS was significantly lower in NALP3-/-,ASC-/- cells compared to control cells.Our study demonstrates that NALP3/Asc plays role in maturation,differentiation and function of mast cells in vitro.
Original languageEnglish
Publication statusPublished - 1 Apr 2011

Keywords

  • inflammasome
  • cytokine
  • interleukin 1
  • interleukin 6
  • caspase
  • receptor
  • immunoglobulin E
  • mast cell
  • maturation
  • bone marrow cell
  • degranulation
  • stimulation
  • in vitro study
  • pathogenesis
  • signal transduction
  • asthma
  • effector cell
  • immunosurveillance
  • wild type
  • mouse
  • cell maturation
  • lung disease

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