TY - JOUR
T1 - Involvement of UVB-induced reactive oxygen species in TGF-β biosynthesis and activation in keratinocytes
AU - Wang, Hongjun
AU - Kochevar, Irene E.
PY - 2005/4/1
Y1 - 2005/4/1
N2 - TGF-β produced by keratinocytes in response to UVB (290-320 nm) is a potential mediator for effects of acute and chronic solar radiation on skin. This study was designed to determine whether reactive oxygen species (ROS) mediate UVB-induced TGF-β biosynthesis in keratinocytes and the subsequent activation of the latent TGF-β complex. UVB irradiation elevated both total (latent plus active) and active TGF-β in the keratinocyte supernatants, with a greater increase in the active form. UVB irradiation induced up to a 30% increase in ROS, and the ROS were detected up to 90 min after irradiation. NAC and Trolox, cytoplasmic ROS scavengers, abolished the UVB-induced TGF-β and intracellular ROS, suggesting that UVB-induced ROS are involved in TGF-β regulation. Inhibitors of NADPH oxidase activity, DPI and apocynin, decreased UVB-induced ROS. The increase in NADPH oxidase activity was mediated by EGFR activation. UVB-induced ROS also activated latent TGF-β complex by stimulating MMP-2 and -9 activities. In summary, physiological doses of UVB increase intracellular ROS, which upregulate TGF-β biosynthesis and activation of TGF-β through increased activity of MMPs.
AB - TGF-β produced by keratinocytes in response to UVB (290-320 nm) is a potential mediator for effects of acute and chronic solar radiation on skin. This study was designed to determine whether reactive oxygen species (ROS) mediate UVB-induced TGF-β biosynthesis in keratinocytes and the subsequent activation of the latent TGF-β complex. UVB irradiation elevated both total (latent plus active) and active TGF-β in the keratinocyte supernatants, with a greater increase in the active form. UVB irradiation induced up to a 30% increase in ROS, and the ROS were detected up to 90 min after irradiation. NAC and Trolox, cytoplasmic ROS scavengers, abolished the UVB-induced TGF-β and intracellular ROS, suggesting that UVB-induced ROS are involved in TGF-β regulation. Inhibitors of NADPH oxidase activity, DPI and apocynin, decreased UVB-induced ROS. The increase in NADPH oxidase activity was mediated by EGFR activation. UVB-induced ROS also activated latent TGF-β complex by stimulating MMP-2 and -9 activities. In summary, physiological doses of UVB increase intracellular ROS, which upregulate TGF-β biosynthesis and activation of TGF-β through increased activity of MMPs.
KW - Free radicals
KW - Human keratinocytes
KW - Reactive oxygen species
KW - Transforming growth factor-β activation
KW - UVB radiation
UR - http://www.scopus.com/inward/record.url?scp=14644397946&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=14644397946&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2004.12.005
DO - 10.1016/j.freeradbiomed.2004.12.005
M3 - Article
C2 - 15749385
AN - SCOPUS:14644397946
SN - 0891-5849
VL - 38
SP - 890
EP - 897
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
IS - 7
ER -