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TNFα receptor endocytosis balances inflammatory and apoptotic signaling in endothelial cells
Author(s) -
Choi Hyehun,
Lamb Fred S
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.924.10
Subject(s) - endocytosis , p38 mitogen activated protein kinases , tumor necrosis factor alpha , microbiology and biotechnology , apoptosis , chemistry , signal transduction , receptor , mapk/erk pathway , endocrinology , biology , biochemistry
Tumor necrosis factor‐α (TNFα) impairs endothelial cell (EC)‐dependent vasodilation. It is not known how endocytosis affects apoptotic vs. proliferative effects of TNFα. We hypothesized that receptor endocytosis modulates the response of ECs to TNFα and impaired vascular relaxation is mediated by MAPK. Mesenteric resistance arteries from C57BL/6 mice were treated with TNFα and selective inhibitors (Dynasore for endocytosis, SP600125 for JNK, SB203580 for p38) for 24hrs and vasodilation was assessed. TNFα impaired acetylcholine (ACh)‐induced relaxation and this effect is exacerbated by Dynasore (Fig. 1, n=6). These effects were JNK and p38‐dependent (Fig. 2, n=6). In cultured mesenteric ECs, TNFα induced JNK, p38, and ERK1/2 phosphorylation but only JNK and p38 activation were potentiated by Dynasore (p‐JNK, 2‐fold; p‐p38, 1.4‐fold; n=3). Thus TNFα‐induced endothelial dysfunction is endocytosis, JNK or p38‐dependent. TNFα receptor endocytosis balances pro‐inflammatory with pro‐apoptotic (JNK, p38) signaling in ECs.