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-18- Photobiology(1) 9/4 Room-B
ULTRAVIOLET B RADIATION UP-REGULATES THE EXPRESSION OF MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF) IN HUMAN EPIDERMAL KERATINOCYTES.
Tadamichi Shimizu1, Riichiro Abe1, Akira Ohkawara1, Jun Nishihira2.
1Department of Dermatology, School of Medicine, 2Central Research Institute, School of Medicine, Hokkaido University, Sapporo, Japan.
Macrophage migration inhibitory factor (MIF) was the first lymphokine reported in the guinea pig to prevent the migration of macrophage out of capillary tubes. MIF has long been considered to be expressed exclusively in activated T-lymphocytes; however, a recent report indicated that macrophages are another major source of MIF. Previously, we demonstrated the presence and tissue localization of MIF in human skin, especially in the basal layer. Ultraviolet B (UVB) radiation has multiple effects within the skin and beyond. Supernatants derived from cultured human epidermal keratinocytes and human epidermal sheets were tested in a MIF-specific bioassay. After stimulation with UVB light, significant amounts of MIF in supernatants were detected, compared to that of untreated keratinocytes. These biological data were also confirmed by Northern blot analysis and immunohistochemical analysis. These finding indicate that human keratinocytes upon stimulation by UVB are capable to synthesize and release MIF. It is suggested that MIF may mediate skin inflammatory reactions during host defense against such as UVB radiation.
-19- Photobiology(1) 9/4 Room-B
ULTRAVIOLET RADIATION REDUCES C3 PRODUCTION BY HUMAN CULTURED EPIDERMAL KERATINOCYTES IN RESPONSE TO IFNg OR TNFa.
Tadashi Terui, Michitaka Funayama, Maki Ozawa, Taizo Kato, Hachiro Tagami.
Department of Dermatology, Tohoku University School of Medicine, Sendai, Japan.
BACKGROUND: We have demonstrated that C5a plays a role in the formation of sterile pustules in psoriasis and its related skin diseases. However, it remains to be elucidated how complement activation occurs in the lesional skin. Recently, we have reported that IFNg and TNFa can augment the production of C3, the key complement component, by human cultured epidermal keratinocytes. PURPOSE: The present study is designed to investigate whether prior UV radiation affects the C3 production by the keratinocytes in response to IFNg and/or TNFa. METHODS: Keratinocytes cultured in serum-free medium were exposed to various doses of UVB, UVA, or UVA after their pretreatment with psolaren. C3 production was assessed by a ELISA method and RT-PCR. RESULTS: UV exposure resulted in the reduction of the C3 production by the keratinocytes. Among the 3 UV sources, PUVA was the most effective inhibitor. CONCLUSION: The results of this study suggest that UV radiation exerts a beneficial effect in the treatment of psoriasis and the related diseases partly through the inhibition of local production of C3 that is required for the maximum complement activation in the lesional skin.
-20- Photobiology(1) 9/4 Room-B
THE ROLE OF TNF-a IN SUNBURN CELL FORMATION IN A SKIN ORGAN CULTURE SYSTEM.
Koichi Nakagawa, Tatsuya Horikawa, and Masamitsu Ichihashi.
Department of Dematology, Kobe University School of Medicine, Kobe , Japan.
It is well known that ultraviolet (UV) radiation induces sunburn cell formation in vivo and that TNF-a plays a partial role in the induction of apoptosis of cultured keratinocytes. Here we developed a new experimental method for studying sunburn cell formation using a skin organ culture system. induced Sunburn cells were induced by UVB irradiation in this skin organ culture system. Using this system we investigated a role of TNF-a in sunburn cells formation by UVB irradiation. We found that pentoxifyllin which is known to inihbit TNFa production, remarkably reduced the formation of sunburn cells by UVB irradiation. We also confirmed that pentoxifyllin inhibited the release of TNF-a into the culture media after UVB irradition. These results suggest that TNF-a plays an important role in the induction of sunburn cells.
-21- Photobiology(1) 9/4 Room-B
ANALYSIS OF MOLECULAR MECHANISM OF SUNBURN CELL FORMATION INDUCED BY UV IRRADIATION.
Yoko Abe, Masako U Udono, Ichiro Katayama.
Department of Dermatology, Nagasaki University School of Medicine, Nagasaki, Japan.
We have previously observed that UV-irradiation induced cyclobutane-type pyrimidine dimers (CPD) and simultaneous accumulation of p53 protein in the nuclei of human epidermal cells in vivo. Based on the evidence that morphological similarity was observed between sunburn cell and apoptotic cell ,we further examined whether sunburn cells resulted from impaired CPD repair followed by apoptosis via p53 dependent pathway. Enzyme labeled antibody method with monoclonal antibody against CPD (TDM-2)detected CPD formation in the sunburn cells.Whether apoptosis was induced in these cells,was analyzed by TUNNEL method.
-22- Photobiology(1) 9/4 Room-B
INDUCED EXPRESSION OF p16 PROTEIN IN UVB-IRRADIATED NORMAL HUMAN EPIDERMIS AND CULTURED KERATINOCYTES.
Ahmed U. Nazim, Masato Ueda, Masamitsu Ichihashi.
Department of Dermatology, Kobe University School of Medicine, Kobe, Japan.
P16INK4a, the product of cyclin-dependent kinase inhibitor 2 (CDKN2) gene prevents phosphorylation of retinoblastoma protein (pRb), and thus acts as a negative cell cycle regulator. To know the effect of UVB irradiation on p16 protein expression, an immunohistochemical and western blot analysis were performed on paraffin section of UVB-irradiated normal human epidermis and cultured keratinocytes, respectively. Control epidermal cells showed none or little p16 specific staining. An increased level of p16 protein was observed in UVB-irradiared epidermis in a time dependent manner. p16 protein started to be elevated at 48 h after UVB irradiation, peaked at 72-120 h and that overexpression continued until 168 h of post-irradiation. Stained cells were distributed mainly in the lower epidermis with reaction product seen within nucleus or within the nucleus and cytoplasm. Western blot analysis of p16 confirmed the immunohistochemical observations. Our results suggest that p16 protein expression may have a significant role for the response to UVB irradiation in human skin.
-23- Photobiology(1) 9/4 Room-B
EFFECTS OF NEAR-INFRARED RADIATION ON EPIDERMAL PROLIFERATION AND IMMUNE FUNCTION OF THE SKIN.
Noriko Mori, Nobuo Sugie, Kiichiro Danno.
Department of Dermatology, Shiga University of Medical Science, Otsu, Japan.
While UV light alters various cutaneous cell function, little is known about the biological action of infrared (IR) radiation except increased skin temperature. This study examined effects of near-IR (800 - 1500 nm) on the epidermal proliferation rate, Langerhans cell (LC) counts, and contact hypersensitivity reaction (CHS) in mice. Near IR caused a reversible suppression to BrdU+ cells, ADPase+ LC counts , and DNFB-induced CHS. The results suggest that near IR, like effects by UV light, modulates epidermal proliferation and part of immune function of skin.