NFκB attenuates IL-5 production and upregulates T-box transcription factors in Th2-like T cells.

Abstract:

:IL-5 plays important roles in eosinophil differentiation, expansion, and recruitment. The regulation of IL-5 seems critical for the treatment of eosinophil-mediated allergic reactions. However, the precise mechanisms for IL-5 regulation remain unknown. In this study, we investigated how IL-5 production is regulated. The transduction of GATA-3 into a murine T cell hybridoma resulted in acquiring the ability to produce IL-5 in response to an antigenic stimulus like Th2 cells. This production was dependent on the cAMP-PKA pathway, but not on p38 activation. Transduction of NIK largely impaired IL-5 production. RelA and RelB similarly impaired IL-5 production. RelA decreased not only IL-5 protein amount but mRNA. RelA also inhibited Il5-luciferase reporter activity. The transduction of GATA-3 decreased the expression of Tbx21 and Eomes, but the additional transduction of RelA abrogated the decreased expression of GATA-3-induced Tbx21 and Eomes. Furthermore, the transduction of T-bet or Eomes into the GATA-3-transduced T cell hybridoma impaired IL-5 production. These results suggested that strong enhancement of the NFκB pathway downregulates IL-5 production and upregulates T-box protein expression to shift an immune response from Th2 to inflammatory Th1.

journal_name

Cytotechnology

journal_title

Cytotechnology

authors

Hashiguchi M,Kobayashi A,Kashiwakura Y,Kojima H,Kanno Y,Kurosu A,Tokudome S,Kobata T

doi

10.1007/s10616-013-9585-z

subject

Has Abstract

pub_date

2014-05-01 00:00:00

pages

373-82

issue

3

eissn

0920-9069

issn

1573-0778

journal_volume

66

pub_type

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