IL-1β transcript stability in monocytes is linked to cytoskeletal reorganization and the availability of mRNA degradation factors

Monocyte extravasation initiates reorganization of the cytoskeleton (CSK) and adhesion-dependent cytokine gene transcription. The actin CSK is thought to be crucial for compartmentalization and translation of mRNA, many of which contain AU-rich (ARE) instability motifs in the 3′ untranslated region. We investigated regulation of adhesion-induced IL-1β expression by the monocyte CSK. In serum-free adherent monocytes, the induced IL-1β mRNA was stable and did not coextract with actin filaments. In contrast, in cells adherent in autologous serum, IL-1β transcripts were unstable, coextracted with actin filaments and were associated with only transient activation of the mitogen-activated protein kinases (MAPK). Under both conditions of adherence, the ARE-binding protein AUF1/hnRNP D was readily extracted in the cytosolic fraction. Electro-injection with AUF1/hnRNP D modified the actin CSK and, surprisingly, stabilized IL-1β transcripts. These data suggest that the control of mRNA degradation is linked with changes in the CSK. Mitogen-activated protein kinase activation or alterations in the availability of mRNA degradation factors may mediate these effects.