NDLI: Selective inhibition of the FcɛRI-induced de novo synthesis of mediators by an inhibitory receptor

Content Provider	PubMed Central
Author	Abramson, Jakub Licht, Arieh Pecht, Israel
Copyright Year	2006
Abstract	Aggregation of the type 1 Fcɛ receptors (FcɛRI) on mast cells initiates a network of biochemical processes culminating in secretion of both granule-stored and de novo-synthesized inflammatory mediators. A strict control of this response is obviously a necessity; nevertheless, this regulation is hardly characterized. Here we report that a prototype inhibitory receptor, the mast cell function-associated antigen (MAFA), selectively regulates the FcɛRI stimulus–response coupling network and the subsequent de novo production and secretion of inflammatory mediators. Specifically, MAFA suppresses the PLC-γ2–[Ca2+]i, Raf-1–Erk1/2, and PKC–p38 coupling pathways, while the Fyn–Gab2-mediated activation of PKB and Jnk is essentially unaffected. Hence, the activities of several transcription/nuclear factors for inflammatory mediators (NF-κB, NFAT) are markedly reduced, while those of others (Jun, Fos, Fra, p90rsk) are unaltered. This results in a selective inhibition of gene transcription of cytokines including IL-1β, IL-4, IL-8, and IL-10, while that of TNF-α, MCP-1, IL-3, IL-5, or IL-13 remains unaffected. Taken together, these results illustrate the capacity of an immunoreceptor tyrosine-based inhibitory motif-containing receptor to cause tight and specific control of the production and secretion of inflammatory mediators by mast cells.
Related Links	http://dx.doi.org/10.1038/sj.emboj.7600932
Ending Page	334
Page Count	12
Starting Page	323
File Format	PDF
ISSN	02614189
e-ISSN	14602075
Journal	The EMBO Journal
Issue Number	2
Volume Number	25
Language	English
Publisher Date	2006-01-25
Access Restriction	Open
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Immunology and Microbiology(all) Neuroscience(all) Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Neuroscience Immunology and Microbiology Medicine Molecular Biology

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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