Involvement of P38 MAP kinase in the augmentation of UVB-mediated apoptosis via the epidermal platelet-activating factor receptor.
Platelet-activating factor (PAF) is a group of phosphocholines with various biological effects, which are mediated by the PAF receptor (PAF-R). Our previous studies have demonstrated that ultraviolet B radiation (UVB) is a potent stimulus for PAF production, and that the presence of the PAF-R on epithelial cells results in an augmentation of UVB-induced apoptosis. Inasmuch as PAF-R activation results in numerous signal transduction pathways, the present study was designed to characterize the signal transduction pathway responsible for PAF-R-mediated enhanced UVB-induced cytotoxicity. Using a model system of PAF-R-negative and -positive epithelioid KB cells, we demonstrate that inhibitors of p38 MAP kinase block the augmentation of UVB-mediated apoptosis seen in PAF-R-positive KB cells. In contrast, pharmacological and/or molecular inhibition of other pathways linked to PAF-R activation including ERK MAP kinase and NFkappaB do not affect PAF-R-mediated cytotoxicity. This study demonstrates the important role that p38 MAP kinase plays in PAF-R-mediated augmentation of UVB cytotoxicity.
Landis
Megan
M
Department of Dermatology, H. B. Wells Center for Pediatric Research, James Whitcomb Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Yi
Qiaofang
Q
Hyatt
Ann-Marie
AM
Travers
Angela R
AR
Lewis
Davina A
DA
Travers
Jeffrey B
JB
D017209:Apoptosis / Q000502:physiology* / Q000528:radiation effects; D004817:Epidermis / Q000473:pathology* / Q000528:radiation effects; D006801:Humans; D007624:KB Cells; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction / Q000528:radiation effects; D014466:Ultraviolet Rays; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D048051:p38 Mitogen-Activated Protein Kinases