Extracellular IL-33 cytokine, but not endogenous nuclear IL-33, regulates protein expression in endothelial cells.
IL-33 is a nuclear cytokine from the IL-1 family that plays important roles in health and disease. Extracellular IL-33 activates a growing number of target cells, including group 2 innate lymphoid cells, mast cells and regulatory T cells, but it remains unclear whether intracellular nuclear IL-33 has additional functions in the nucleus. Here, we used a global proteomic approach based on high-resolution mass spectrometry to compare the extracellular and intracellular roles of IL-33 in primary human endothelial cells, a major source of IL-33 protein in human tissues. We found that exogenous extracellular IL-33 cytokine induced expression of a distinct set of proteins associated with inflammatory responses in endothelial cells. In contrast, knockdown of endogenous nuclear IL-33 expression using two independent RNA silencing strategies had no reproducible effect on the endothelial cell proteome. These results suggest that IL-33 acts as a cytokine but not as a nuclear factor regulating gene expression in endothelial cells.
Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, Toulouse, France.
Violette
V
Gautier
Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, Toulouse, France.
Corinne
C
Cayrol
Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, Toulouse, France.
Dorian
D
Farache
Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, Toulouse, France.
Stéphane
S
Roga
Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, Toulouse, France.
Bernard
B
Monsarrat
Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, Toulouse, France.
Odile
O
Burlet-Schiltz
Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, Toulouse, France.
Anne
A
Gonzalez de Peredo
Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, Toulouse, France.
Jean-Philippe
JP
Girard
D002467:Cell Nucleus / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D000067596:Interleukin-33 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012313:RNA / Q000235:genetics; D053719:Tandem Mass Spectrometry
C506536:IL33 protein, human; D018836:Inflammation Mediators; D000067596:Interleukin-33; D012313:RNA
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