Jen, Ku Sheau
(2004)
Expression of the transcription factor,
PPAR in human monocytes.
Masters thesis, Universiti Sains Malaysia.
Abstract
The peroxisome proliferator-activated receptors (PPARs) are members of the
nuclear hormone receptor superfamily of transcription factor that mediate liganddependent
transcriptional activation and repression. They regulate genes associated
with lipid and glucose metabolism. Recent evidence suggests that PPARs may also
act as a negative immunomodulator. To investigate the potential role of PPARa, y1
and y2 in regulating inflammation mediated by monocyte, the expression of PPARa,
y1 and y2 in lipopolysaccharide (LPS)-activated and non-activated human monocytes
was quantified.
Monocytes secrete inflammatory cytokines such as interleukin (IL)-1 ~' IL-6 and
tumor necrosis factor (TNF)-a in response to LPS. To verify stimulation of monocytes
by LPS, various cytokines including granulocyte/macrophage colony-stimulating
factor (GM-CSF), TN F-a, IL-1 ~' IL-6, IL-8 and transforming growth factor (TGF)J3
expression of LPS-activated and non-activated human monocytes was analyzed by
using multiplex PCR and their expression is normalized against glyceraldehyde-3-
phosphate dehydrogenase (GAPDH) expression. All these inflammatory cytokine
expressions were increased in LPS-activated monocytes compared to non-activated
monocytes.
Measurement of the gene expression levels of PPARa, PPARy1 and PPARy2
in both LPS-activated and non-activated monocytes was carried out using Real-Time
PCR analysis. The study showed that LPS induced expression of both PPARa and
PPARy2 in isolated human monocytes with a preferential upregulation of PPARy2.
The PPARy1 however was not expressed in both LPS-activated and non-activated
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