Ultraviolet light and interleukin-10 modulate expression of cytokines by transformed human dermal microvascular endothelial cells (HMEC-1).
Exposure of the skin to ultraviolet (UV) light causes DNA damage, inflammation, and impairment of local as well as systemic immune responses. Dermal microvascular endothelial cells are key elements for the recruitment of inflammatory cells during the pathogenesis of inflammatory skin diseases via the expression of adhesion molecules and the release of cytokines. Because UVB may directly affect the function of dermal cells it was investigated whether UVB irradiation alters the production of proinflammatory and chemotactic cytokines by endothelial cells. UVB exposure of transformed human microvascular endothelial cells (HMEC-1) resulted in a dose dependently increased mRNA expression as well as release of interleukin (IL)-1beta, IL-6, IL-8, and growth-regulated oncogene alpha (GROalpha). Maximum cytokine production was observed 16-24 h after irradiation when 7.5-12.5 mJ UVB per cm2 were used. In addition, it was examined whether IL-10, which is upregulated in keratinocytes following UVB irradiation and accounts for UV mediated immunosuppression such as inhibition of contact hypersensitivity, also affects endothelial cell cytokine production. Treatment of HMEC-1 with IL-10 significantly enhanced IL-6 and IL-8 release and further upregulated UVB-induced IL-6 and IL-8 mRNA expression. These findings demonstrate that UVB both directly and indirectly via the release of IL-10 stimulates microvascular endothelial cells to produce proinflammatory cytokines and chemokines that are required for the migration and activation of inflammatory cells in UV-mediated inflammatory skin reactions.
Ludwig Boltzmann Institute for Cell Biology and Immunobiology of the Skin, Department of Dermatology, University of Münster, Germany.
T
T
Scholzen
M
M
Hartmeyer
M
M
Fastrich
T
T
Brzoska
E
E
Becher
T
T
Schwarz
T A
TA
Luger
D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D016753:Interleukin-10 / Q000494:pharmacology*; D016209:Interleukin-8 / Q000096:biosynthesis; D008833:Microcirculation / Q000378:metabolism; D012867:Skin / Q000098:blood supply*; D014466:Ultraviolet Rays
D016207:Cytokines; D016209:Interleukin-8; D016753:Interleukin-10; D006861:Hydrogen Peroxide