How adhesion, migration, and cytoplasmic calcium transients influence interleukin-1beta mRNA stabilization in human monocytes.
We investigated the mechanisms by which primary human monocyte migration and the production of important cytokines are co-regulated. Motile monocytes underwent cyclic morphologic and adhesive changes that were associated with intracellular free calcium changes; in such cells, cytokine transcripts were unstable and translationally repressed. Agents that activate monocytes, including lipopolysacharrides (LPS), cytomegalovirus (CMV), and tumor necrosis factor (TNFalpha), have been shown to de-repress translation and these agents stabilize adhesion-induced transcripts for IL-lbeta and IL-8 and markedly diminish cell migration in the presence of autologous serum. LPS suppressed Rho A activity and either this agent or C3 transferase elevated intracellular free calcium, stabilized transcripts, and, in tandem, inhibited cell migration by preventing tail retraction, a prerequisite for cell translocation. These results, therefore, suggest that monocyte activating agents inhibit the RhoA pathway and continuously elevate intracellular calcium leading to a concomitant decrease in monocyte migration and stabilization of cytokine transcripts prior to translation.
Pomorski
P
P
Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, 27599, USA.
Watson
J M
JM
Haskill
S
S
Jacobson
K A
KA
D036002:ADP Ribose Transferases / Q000633:toxicity; D001905:Botulinum Toxins / Q000633:toxicity; D002118:Calcium / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity; D008213:Lymphocyte Activation / Q000187:drug effects; D009000:Monocytes / Q000378:metabolism; D020871:RNA Stability / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D016207:Cytokines; D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D001905:Botulinum Toxins; D020742:rhoA GTP-Binding Protein; D002118:Calcium