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

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

Evaluating active labor market programs in Romania

Active labor market programs, Propensity score matching, Transition economies, Pre-program employment information, J21, J31, J64, J65, J68,

The Absence of the African-American Owned Business: An Analysis of the Dynamics of Self-Employment

Estimates from the Panel Study of Income Dynamics (PSID) indicate that African-American men are one-third as likely to be self-employed as white men.  The large discrepancy is due to a black transition rate into self-employment that is approximately one half the white rate and a black transition rate out of self-employment that is twice the white rate.  Using a new variation of the Blinder-Oaxaca decomposition technique, I find that racial differences in asset levels and probabilities of having self-employed fathers explain a large part of the black/white gap in the entry rate, but almost none of the gap in the exit rate