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 language | English (US) |
|---|---|
| Pages (from-to) | 91-97 |
| Number of pages | 7 |
| Journal | Clinical and Developmental Immunology |
| Volume | 12 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jun 2005 |
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Keywords
- Cytokine
- Interleukin
- Phoca vitulina
- Polychlorinated biphenyl
- Polycyclic aromatic hydrocarbon
- Protein tyrosine kinase
ASJC Scopus subject areas
- Immunology
- Cell Biology
- Developmental Biology
Cite this
PAH- and PCB-induced alterations of protein tyrosine kinase and cytokine gene transcription in harbor seal (Phoca vitulina) PBMC. / Neale, Jennifer C C; Kenny, Thomas P.; Tjeerdema, Ronald S.; Gershwin, M. Eric.
In: Clinical and Developmental Immunology, Vol. 12, No. 2, 06.2005, p. 91-97.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - PAH- and PCB-induced alterations of protein tyrosine kinase and cytokine gene transcription in harbor seal (Phoca vitulina) PBMC
AU - Neale, Jennifer C C
AU - Kenny, Thomas P.
AU - Tjeerdema, Ronald S.
AU - Gershwin, M. Eric
PY - 2005/6
Y1 - 2005/6
N2 - 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.
AB - 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.
KW - Cytokine
KW - Interleukin
KW - Phoca vitulina
KW - Polychlorinated biphenyl
KW - Polycyclic aromatic hydrocarbon
KW - Protein tyrosine kinase
UR - http://www.scopus.com/inward/record.url?scp=24744441951&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=24744441951&partnerID=8YFLogxK
U2 - 10.1080/17402520500116624
DO - 10.1080/17402520500116624
M3 - Article
C2 - 16050139
AN - SCOPUS:24744441951
VL - 12
SP - 91
EP - 97
JO - Journal of Immunology Research
JF - Journal of Immunology Research
SN - 2314-8861
IS - 2
ER -