Augmentation of UVB radiation-mediated early gene expression by the epidermal platelet-activating factor receptor.
UVB radiation (UVB) is a known inducer of many biological changes in human skin, and triggers the production of glycerophosphocholines that act as platelet-activating factor (PAF) agonists. To gain a better insight into the role of the epidermal PAF receptor (PAF-R) in UVB-mediated gene expression, Affymetrix oligonucleotide microarrays were used to compare mRNA expression in the PAF-R-negative epithelial cell line KB-expressing PAF-Rs (KBP) with that in KB cells transduced with a vector control (KBM). Total RNA was isolated from KB cells 1 hour after treatment with a PAF-R agonist or UVB irradiation. Treatment of KBP with PAF agonist resulted in altered expression of 220 genes, including cytokines and growth factors. UVB irradiation of KB cells resulted in an increased expression of genes in both cell types. A panel of genes including cytokines CCL20 (MIP3alpha) and tumor necrosis factor-alpha (TNF-alpha) were upregulated selectively in KBP cells and are also selectively upregulated in response to PAF agonist. Consistent with these in vitro findings, UVB irradiation resulted in increased levels of epidermal CCL20 and TNF-alpha mRNA in wild-type over PAF-R-deficient mice in vivo. These studies provide evidence that the epidermal PAF-R can modulate UVB-mediated early gene expression.
Travers
Jeffrey B
JB
Department of Dermatology, H.B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. jtravers@iupui.edu
Edenberg
Howard J
HJ
Zhang
Qiwei
Q
Al-Hassani
Mohammed
M
Yi
Qiaofang
Q
Baskaran
Sulochanadevi
S
Konger
Raymond L
RL
D000818:Animals; D002460:Cell Line; D054418:Chemokine CCL20 / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D005786:Gene Expression Regulation / Q000528:radiation effects*; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D020411:Oligonucleotide Array Sequence Analysis; D010980:Platelet Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014466:Ultraviolet Rays
C108355:CCL20 protein, human; C493447:CCL20 protein, mouse; D054418:Chemokine CCL20; D019402:Macrophage Inflammatory Proteins; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; D014409:Tumor Necrosis Factor-alpha; C039351:platelet activating factor receptor