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

• Main Authors: Jennifer C C Neale, Thomas P Kenny, Ronald S Tjeerdema, & M Eric Gershwin
• Other Authors: The Pennsylvania State University CiteSeerX Archives
• Format: Text
• Language: English
• Subjects: Fyn; harbor seal; Phoca vitulina
• Online Access: http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.1082.7081; http://downloads.hindawi.com/journals/jir/2005/786243.pdf

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 0 ,4,4 0 ,5,5 0 -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.