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Interleukin‐33 drives a proinflammatory endothelial activation that selectively targets non‐quiescent cells
Author(s) -
Haraldsen Guttorm
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.648.1
Subject(s) - proinflammatory cytokine , microbiology and biotechnology , chemokine , umbilical vein , interleukin , signal transduction , biology , cell adhesion molecule , endothelial stem cell , interleukin 8 , interleukin 33 , endogeny , chemistry , immunology , cytokine , inflammation , in vitro , endocrinology , biochemistry
Interleukin‐33 is an alarmin released from stressed or damaged cells. We investigated the effects of interleukin (IL)‐33 on human umbilical vein endothelial cells comparing it to IL‐1β and observing highly similar phosphorylation of signaling molecules and transcription profiles. On the other hand, intradermally injected IL‐33 elicited significantly less endothelial activation when compared to IL‐1β and led us to observe that quiescent endothelial cells (ppRb low p27 high ) were strikingly resistant to IL‐33. Accordingly, the IL‐33 receptor was preferentially expressed in non‐quiescent cells, corresponding to selective induction of adhesion molecules and chemokines. Multiparameter phosphoflow cytometry confirmed that signaling driven by IL‐33 was stronger in non‐quiescent cells. Manipulation of nuclear IL‐33 expression by siren or adenoviral transduction revealed no functional link between nuclear, endogenous IL‐33 and exogenous IL‐33‐responsiveness. We conclude that in contrast to other inflammatory cytokines IL‐33 selectively targets non‐quiescent endothelial cells. By this novel concept quiescent cells may remain non‐responsive to a proinflammatory stimulus that concomitantly triggers a powerful response in cells that have been released from contact inhibition.