title: PAH- and PCB-induced alterations of protein tyrosine kinase and cytokine gene transcription in harbor seal (Phoca vitulina) PBMC.
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.
authors.affiliation: Division of Rheumatology, Allergy, and Clinical Immunology, University of California, One Shields Avenue, Davis, CA, 95616, USA. jcneale@ucdavis.edu
authors.forename: Jennifer C C
authors.initials: JC
authors.lastname: Neale
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Kenny
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Tjeerdema
authors.forename: M Eric
authors.initials: ME
authors.lastname: Gershwin
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D004785:Environmental Pollutants / Q000494:pharmacology*; D005260:Female; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D046049:Phoca; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D011084:Polycyclic Aromatic Hydrocarbons / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects* / Q000276:immunology*
chemical_list: D016207:Cytokines; D004785:Environmental Pollutants; D011084:Polycyclic Aromatic Hydrocarbons; D011078:Polychlorinated Biphenyls; D011505:Protein-Tyrosine Kinases