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TNFα alters occludin and cerebral endothelial permeability: Role of p38MAPK

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  • Yawen Ni
  • Tao Teng
  • Runting Li
  • Agnes Simonyi
  • Grace Y Sun
  • James C Lee

Abstract

Occludin is a key tight junction (TJ) protein in cerebral endothelial cells (CECs) playing an important role in modulating blood-brain barrier (BBB) functions. This protein (65kDa) has been shown to engage in many signaling pathways and phosphorylation by both tyrosine and threonine kinases. Despite yet unknown mechanisms, pro-inflammatory cytokines and endotoxin (lipopolysaccharides, LPS) may alter TJ proteins in CECs and BBB functions. Here we demonstrate the responses of occludin in an immortalized human cerebral endothelial cell line (hCMEC/D3) to stimulation by TNFα (10 ng/mL), IL-1β (10 ng/mL) and LPS (100 ng/mL). Exposing cells to TNFα resulted in a rapid and transient upward band-shift of occludin, suggesting of an increase in phosphorylation. Exposure to IL-1β produced significantly smaller effects and LPS produced almost no effects on occludin band-shift. TNFα also caused transient stimulation of p38MAPK and ERK1/2 in hCMEC/D3 cells, and the occludin band-shift induced by TNFα was suppressed by SB202190, an inhibitor for p38MAPK, and partly by U0126, the MEK1/2-ERK1/2 inhibitor. Cells treated with TNFα and IL-1β but not LPS for 24 h resulted in a significant (p

Suggested Citation

  • Yawen Ni & Tao Teng & Runting Li & Agnes Simonyi & Grace Y Sun & James C Lee, 2017. "TNFα alters occludin and cerebral endothelial permeability: Role of p38MAPK," PLOS ONE, Public Library of Science, vol. 12(2), pages 1-20, February.
    • Handle: RePEc:plo:pone00:0170346
    DOI: 10.1371/journal.pone.0170346
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    1. Grace Y Sun & Zihong Chen & Kimberly J Jasmer & Dennis Y Chuang & Zezong Gu & Mark Hannink & Agnes Simonyi, 2015. "Quercetin Attenuates Inflammatory Responses in BV-2 Microglial Cells: Role of MAPKs on the Nrf2 Pathway and Induction of Heme Oxygenase-1," PLOS ONE, Public Library of Science, vol. 10(10), pages 1-20, October.
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