IL-33 and ST2 comprise a critical biomechanically induced and cardioprotective signaling system
J. Clin. Invest. Shoji Sanada, et al. 117:1538 doi:10.1172/JCI30634 [Go to this article.]

Figure 3
IL-33 transiently activates NF-κB but blocks NF-κB activation by hypertrophic stimuli. (A and B) NF-κB nuclear binding activity measured by EMSA in cardiomyocytes (A) and cardiac fibroblasts (B). (C and D) IκBα phosphorylation evaluated by Western analysis in cardiomyocytes (C) and cardiac fibroblasts (D). Values are relative to control density and are expressed as percent increase compared with control. Both angiotensin II and phenylephrine significantly activated NF-κB. IL-33 also activated NF-κB, but IL-33 markedly attenuated angiotensin II– and phenylephrine-induced NF-κB activation in cardiomyocytes, unlike in cardiac fibroblasts. IκBα phosphorylation was similarly affected by IL-33 treatment. (E) IL-33 (10 ng/ml) did not block IκBα phosphorylation (Western analysis) and NF-κB activity (EMSA) induced by PDGF-BB (10 ng/ml) or TNF-α (10 ng/ml), unlike angiotensin II and phenylephrine. (F) Western analysis for MAPKs and Akt in cardiomyocytes. IL-33 (10 ng/ml) activated all MAPKs, generally to a lesser extent than did IL-1β (10 ng/ml). IL-33 attenuated angiotensin II–induced phosphorylation of p38 MAPK and JNK, but not ERK or Akt. Data are from 4–5 sets of experiments. (G and H) GPCR agonist–induced ROS generation, as measured by 2,7-dichlorodihydrofluorecein diacetate, in cardiomyocytes (G) and cardiac fibroblasts (H). Both angiotensin II and phenylephrine significantly induced ROS generation, which was inhibited by IL-33, in cardiomyocytes. These data suggest that IL-33 can inhibit ROS-dependent hypertrophic signals. *P < 0.05 versus baseline; ^#P < 0.05 versus the same treatment group with IL-33.