c-Src Is the primary signaling mediator of polychlorinated biphenyl - Induced interleukin-8 expression in a human microvascular endothelial cell line

Sung Yong Eum, Geun Bae Rha, Bernhard Hennig, Michal J Toborek

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Interleukin-8/CXCL8 (IL-8) is a prominent factor that modulates endothelial cell proliferation, migration, and angiogenesis. Therefore, the present study focused on the regulatory mechanisms of IL-8 expression induced by environmental pollutants such as polychlorinated biphenyls (PCBs). Treatment of human microvascular endothelial cells (HMECs) with specific PCB congener, 2,2′,4,6,6′-pentachlorobiphenyl (PCB 104), dose dependently increased levels of IL-8 mRNA and secreted protein. IL-8-neutralizing antibody inhibited migration of endothelial cells stimulated by conditioned media derived from PCB 104-treated HMECs. Site-directed mutagenesis of the IL-8 promoter- and DNA-binding assays revealed that activator protein 1 (AP-1) and nuclear factor κB (NF-κB) sites are required for PCB 104-induced IL-8 transcription. Most importantly, pharmacological inhibition of Src kinase activity or overexpression of dominant-negative c-src in HMECs resulted in a significant decrease in IL-8 expression and promoter activity. In contrast, ectopic expression of activated c-Src markedly increased promoter activity of IL-8. These stimulatory effects of dominant-positive c-src were abrogated by mutagenesis of AP-1- and NF-κB-binding sites in the IL-8 promoter.

Original languageEnglish
Pages (from-to)311-320
Number of pages10
JournalToxicological Sciences
Volume92
Issue number1
DOIs
StatePublished - Jul 1 2006
Externally publishedYes

Fingerprint

Polychlorinated Biphenyls
Endothelial cells
Interleukin-8
Endothelial Cells
Cell Line
Mutagenesis
Transcription Factor AP-1
Environmental Pollutants
src-Family Kinases
Cell proliferation
Transcription
Conditioned Culture Medium
Site-Directed Mutagenesis
Neutralizing Antibodies
Cell Movement
Assays
Binding Sites
Cell Proliferation
Pharmacology
Messenger RNA

Keywords

  • Angiogenesis
  • AP-1
  • c-Src
  • Endothelial cells
  • IL-8
  • NF-κB
  • PCB

ASJC Scopus subject areas

  • Toxicology

Cite this

c-Src Is the primary signaling mediator of polychlorinated biphenyl - Induced interleukin-8 expression in a human microvascular endothelial cell line. / Eum, Sung Yong; Rha, Geun Bae; Hennig, Bernhard; Toborek, Michal J.

In: Toxicological Sciences, Vol. 92, No. 1, 01.07.2006, p. 311-320.

Research output: Contribution to journalArticle

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