The study of the elements of inflammatory response related with ultraviolet-induced skin carcinogenesis using Xpa knockout mice-the control of inflammation in the skin

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10126
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Kobe University
• Principal Investigator: KUNISADA MAKOTO 神戸大学, 医学部附属病院, 講師 (80566969)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 紫外線皮膚発癌 / 炎症反応 / UVB / CXCL1 / Xpaノックアウトマウス / 活性酸素

Outline of Final Research Achievements

We have already reported that ultraviolet-(UV) induced inflammation might involve the mechanism of UV-induced skin carcinogenesis. We this time utilised Xpa knockout mice, the model of Xeroderma pigmentosum type A that reveal marked increased skin cancer and abnormal inflammatory skin reaction by UV for detecting some important molecules related to this extreme phenotype. We have performed microarray to obtain up-regulated genes in Xpa knockout mice compared to wild-type mice and found CXCL1, that is neutrophils-attractant chemokine was significantly up-regulated in both mRNA and protein level. Furthermore, when we administered the CXCXL1 neutralising antibody with chronic UVB exposure for Xpa knockout mice, the tumor production has been significantly decreased and the induction of skin tumor development also showed delayed compared to the control group. These results suggests that CXCL1 is critical molecule related to UV-induced inflammation as well as skin tumor development.

Free Research Field

紫外線皮膚発癌

Academic Significance and Societal Importance of the Research Achievements

紫外線発癌のメカニズム解明において、紫外線による皮膚の炎症反応が重要な要素であることが証明出来、今後皮膚癌における治療や予防などにおいて抗炎症を考慮した戦略に繋がる可能性が出来た。さらにそれらの炎症反応において活性酸素が重要な要素であることも証明できたので、抗炎症のストラテジーとともに抗酸化作用を考えた内服や外用などの治療応用に発展できる可能性がある。さらに皮膚癌は多段階発癌を経るシステムと考えられているが、そのどのポイントで炎症反応が関与するかをさらに詳細に明らかにすることにより、紫外線皮膚発癌のメカニズム解明が進むことになる。