EGFR activation confers protections against UV-induced apoptosis in cultured mouse skin dendritic cells.
Ultraviolet radiation (UV) induces apoptosis and functional maturation in skin dendritic cells (DCs). However, the molecular mechanisms through which UV activates DCs have not been thoroughly investigated. In this study, we examined the mechanisms of activation and apoptosis of DCs after UV irradiation by focusing on epidermal growth factor receptor (EGFR). Our previous studies have demonstrated that in addition to cognate ligands, EGFR is also activated by UVB irradiation in cultured human skin keratinocytes in vitro and in human skin in vivo. We found for the first time in this study that UV also induces EGFR activation in cultured mouse skin DCs (XS 106 cell line) as well as mouse monocyte-derived dendritic cells (MoDCs). Pharmacological inhibition of EGFR tyrosine kinase significantly inhibits UV-induced ERK, p38, and JNK MAP kinases, and their effectors, transcription factors c-Fos and c-Jun. Inhibition of EGFR also suppresses UV-induced activation of PI3K/AKT/mTOR/S6K and NF-kappaB signal transduction pathways. Our data demonstrated that UV induces LKB1/AMPK pathway, also dependent on EGFR trans-activation. We further observed that MAPK, LKB1/AMPK, PI3K/AKT/mTOR/S6K as well as NF-kappaB activation are impaired in EGFR-/- cells compared to wide type MEF cells after UV radiation. Taken together, we conclude that UV induces multiple signaling pathways mediated by EGFR trans-activation leading to possible maturation, apoptosis and survival, and EGFR activation protects against UV-induced apoptosis in cultured mouse dendritic cells.
Cao
Cong
C
Department of Biology, Providence College, Providence, RI 02918, USA.
Lu
Shan
S
Jiang
Qin
Q
Wang
Wen-Jun
WJ
Song
Xiuzu
X
Kivlin
Rebecca
R
Wallin
Brittany
B
Bagdasarian
Andrew
A
Tamakloe
Tyrone
T
Chu
Wen-Ming
WM
Marshall
John
J
Kouttab
Nicola
N
Xu
Aie
A
Wan
Yinsheng
Y
D055372:AMP-Activated Protein Kinases; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000201:enzymology* / Q000528:radiation effects; D004789:Enzyme Activation / Q000528:radiation effects; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D039642:Eukaryotic Initiation Factors; D006801:Humans; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D009097:Multienzyme Complexes / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000528:radiation effects; D012867:Skin / Q000166:cytology* / Q000201:enzymology; D058570:TOR Serine-Threonine Kinases; D015533:Transcriptional Activation / Q000528:radiation effects; D014466:Ultraviolet Rays
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C499527:Eif4ebp1 protein, mouse; D039642:Eukaryotic Initiation Factors; D009097:Multienzyme Complexes; D016328:NF-kappa B; D010750:Phosphoproteins; D011494:Protein Kinases; C546842:MTOR protein, human; C546843:mTOR protein, mouse; D066246:ErbB Receptors; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases