Abstract
Multifunctional Ca2+/calmodulin‐dependent protein kinase II (CaMKII) is a well‐characterized family of proteins comprised of four separate isoforms: α, β, δ, and γ. These isoforms are differentially expressed in a tissue‐specific manner and contribute to diverse physiological and pathophysiological conditions. However, little is known regarding CaMKII isoform expression and function in the endothelium. Previous data from our lab has shown that CaMKIIδ6 is the primary isoform expressed in human umbilical vein endothelial cells (HUVECs) and promote thrombin‐induced loss of barrier function. Interleukin 6 (IL‐6) is a proinflammatory cytokine that induces loss of barrier function in HUVECs through a JAK/STAT3 signaling cascade. The purpose of this study was to test if CaMKIIδ mediates IL‐6‐induced increase in endothelial barrier permeability. Using qPCR, we determined that CaMKIIδ is the most abundant isoform of the enzyme present in HUVECs. Upon treatment with IL‐6, significant increases in both CaMKIIδ transcription and protein expression were observed. Treatment of HUVECs with JAK inhibitor ruxolitinib and siRNA for STAT3 decreased CaMKIIδ expression. However, adenoviral overexpression of various mutant CaMKII isoforms or siRNA knock down of CaMKIIδ did not affect IL‐6‐dependent loss of barrier function as measured by electric cell‐substrate impedence sensing (ECIS). It has been reported that IL‐6 signaling not only induces a loss of endothelial barrier function, but also increases endothelial cell migration. Indeed, siRNA knock down of CaMKIIδ attenuated IL‐6‐induced endothelial cell migration in a scratch‐wound assay. For the first time, our findings thus far have identified transcriptional induction of CaMKIIδ by IL‐6 that is necessary for the subsequent increase in endothelial cell migration.Support or Funding InformationRO1HL49426‐21 to Harold A. SingerThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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