PAH- and PCB-induced alterations of protein tyrosine kinase and cytokine gene transcription in harbor seal (Phoca vitulina) PBMC

Jennifer C C Neale, Thomas P. Kenny, Ronald S. Tjeerdema, M. Eric Gershwin

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Mechanisms underlying in vitro immunomodulatory effects of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) were investigated in harbor seal peripheral leukocytes, via real-time PCR. We examined the relative genetic expression of the protein tyrosine kinases (PTKs) Fyn and Itk, which play a critical role in T cell activation, and IL-2, a cytokine of central importance in initiating adaptive immune responses. IL-1, the macrophage-derived pro-inflammatory cytokine of innate immunity, was also included as a measure of macrophage function. Harbor seal PBMC were exposed to the prototypic immunotoxic PAH benzo[a]pyrene (BaP), 3,3′,4,4′,5, 5′-hexachlorobiphenyl (CB-169), a model immunotoxic PCB, or DMSO (vehicle control). Exposure of Con A-stimulated harbor seal PBMC to both BaP and CB-169 produced significantly altered expression in all four targets relative to vehicle controls. The PTKs Fyn and Itk were both up-regulated following exposure to BaP and CB-169. In contrast, transcripts for IL-2 and IL-1 were decreased relative to controls by both treatments. Our findings are consistent with those of previous researchers working with human and rodent systems and support a hypothesis of contaminant-altered lymphocyte function mediated (at least in part) by disruption of T cell receptor (TCR) signaling and cytokine production.

Original languageEnglish (US)
Pages (from-to)91-97
Number of pages7
JournalClinical and Developmental Immunology
Volume12
Issue number2
DOIs
StatePublished - Jun 2005

Keywords

  • Cytokine
  • Interleukin
  • Phoca vitulina
  • Polychlorinated biphenyl
  • Polycyclic aromatic hydrocarbon
  • Protein tyrosine kinase

ASJC Scopus subject areas

  • Immunology
  • Cell Biology
  • Developmental Biology

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