English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Transforming growth factor beta is the prototype of a large family of secreted factors that regulate multiple biological processes. In the immune system, TGFbeta acts as an anti-inflammatory and immunosuppressive molecule, whereas the cytokine interleukin (IL)-1beta is a crucial mediator of inflammatory responses and induces proinflammatory genes and acute phase proteins. Here, we present evidence for the existence of a direct inhibitory interaction between the IL-1beta and TGFbeta signaling cascades that is not dependent on IL-1beta-induced SMAD7 expression. IL-1beta and its downstream mediator TAK1 inhibit SMAD3-mediated TGFbeta target gene activation, whereas SMAD3 nuclear translocation and DNA binding in response to TGFbeta are not affected. IL-1beta transiently induces association between TAK1 and the MAD homology 2 domain of SMAD3, resulting in SMAD3 phosphorylation. Furthermore, IL-1beta alleviates the inhibitory effect of TGFbeta on in vitro hematopoietic myeloid colony formation. In conclusion, our data provide evidence for the existence of a direct inhibitory effect of the IL-1beta-TAK1 pathway on SMAD3-mediated TGFbeta signaling, resulting in reduced TGFbeta target gene activation and restored proliferation of hematopoietic progenitors.

Inhibition of the Transforming Growth Factor β (TGFβ) Pathway by Interleukin-1β Is Mediated through TGFβ-activated Kinase 1 Phosphorylation of SMAD3