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UV-induced platelet
activating factor receptor agonists cause immunosuppression.
Nghiem, Dat1,
Walterscheid, Jeffrey1 and Ullrich, Stephen1
The University of Texas M.D. Anderson Cancer Center, Houston, TX 770301
Abstract-
It is generally accepted that prolonged exposure to ultraviolet (UV)
light plays a critical role in the initiation and promotion of non-melanoma
skin cancer. UV also causes antigen-specific, systemic immune suppression.
Studies have shown that UV-induced immune suppression is a risk factor
for skin cancer induction. It is well known that UV irradiation causes
the production and release of serum IL-4 and IL-10. These immunomodulatory
cytokines, particularly IL-10, impair systemic antigen presenting cell
function to type-1 T cells and ultimately suppress the induction of
delayed-type hypersensitivity reactions (DTH). However, the earliest
molecular events that occur after UV exposure are not well defined.
It is known that UV can induce the production of platelet activating
factor (PAF). It is also known that PAF is sufficient to induce the
production of IL-10. In order to understand the primary events of the
immunosuppressive pathway, we studied the effects of phosphatidylcholine
(PC), UV-irradiated PC (UV-PC), and carbamyl-PAF (cPAF) on the DTH response.
When C3H mice are exposed to 10 kJ/m2 of UV radiation, injected with
10 pmol cPAF, or 10 nmol UV-PC, immune suppression of the DTH reaction
was observed. Mice receiving 10 nmol PC generated an immune response
equivalent to the positive controls. Pre-loading mice with 10 nmol PCA-4248,
a PAF receptor (PAFR) antagonist, before UV or before mice received
the PAFR agonists protected against immune suppression. Therefore, we
propose that UV exposure produces PAFR agonists capable of initiating
a signal through the PAFR. This signal ultimately results in the suppression
of cell-mediated immune responses.
Keywords: UV,
DTH, PAF
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