The peroxisome proliferator-activated receptor γ antagonist, GW9962, alters UVB-induced inflammatory responses, apoptosis, and delayed hyperproliferation

Date
2009-01-16T17:25:58Z
Language
American English
Embargo Lift Date
Department
Committee Chair
Degree
M.S.
Degree Year
Department
Department of Pathology & Laboratory Medicine
Grantor
Indiana University
Journal Title
Journal ISSN
Volume Title
Found At
Abstract

It has recently been shown that the gamma subtype of the peroxisome proliferator-activated receptor (PPARγ) is a target of ultraviolet B (290-320 nm; UVB) irradiation, and that PPARγ activation is necessary for full UVB-induced cyclooxygenase-2 (COX-2) induction. However, the biological significance of PPARγ activation in cutaneous photobiology is unknown. Acute UVB irradiation results in a characteristic series of events in the epidermis which includes: an initial edema response and subsequent inflammation, COX-2 induction, apoptosis, and a delayed hyperproliferative response. Therefore, the regulatory role of PPARγ activation was examined in this acute photoresponse using a topical application of the potent, irreversible PPARγ antagonist, GW9962. GW9662 was applied to the epidermis of SKH1 hairless albino mice at increasing doses (0.01-1.0mM) prior to UVB irradiation. The photobiological responses were examined through RT-PCR, skin thickness measurements, and immunohistochemistry, at 24 and 72 hours after UVB-irradiation. At the highest dose, GW9622 significantly inhibited UVB-induced inflammation, as measured by COX-2 induction at both 24 and 72 hrs. Inflammation assessed by skin thickness measurements indicated that lower doses mildly increased inflammation at 72 hrs, but suppressed inflammation at the highest dose. In contrast, GW9662 treatment dose dependently augmented UVB-induced apoptosis at 24 hours, while affecting the delayed hyperproliferative response at 72 hours in an inverse dose-response manner. The results from this study suggest that PPARγ is a key regulator of these photobiological responses. Because these responses are well known to be involved in tumor development and progression, this study also suggests a potential role for PPARγ in UVB-induced skin cancers.

Description
Indiana University-Purdue University Indianapolis (IUPUI)
Keywords
item.page.description.tableofcontents
item.page.relation.haspart
Cite As
ISSN
Publisher
Series/Report
Sponsorship
Major
Extent
Identifier
Relation
Journal
Rights
Source
Alternative Title
Type
Thesis
Number
Volume
Conference Dates
Conference Host
Conference Location
Conference Name
Conference Panel
Conference Secretariat Location
Version
Full Text Available at
This item is under embargo {{howLong}}