Transglutaminase 2 mediates UV-induced skin inflammation by enhancinginflammatory cytokine production

Collection with item attached
2017
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/486447.do
DOI
10.1038/cddis.2017.550
Title
Transglutaminase 2 mediates UV-induced skin inflammation by enhancinginflammatory cytokine production
Description
This work was funded by the National Research Foundation of Republic ofKorea (NRF-2013R1A1A2065273, NRF-2014R1A2A2A01006731, andNRF-2017R1D1A1B03035059), the Korea Healthcare Technology R&D Project,Ministry of Health and Welfare, Republic of Korea (HI14C3339), and theBrain Korea 21 PLUS program of the Korean Ministry of Education, Scienceand Technology.
abstract
UV irradiation elicits acute inflammation in the skin by increasing proinflammatory cytokine production in keratinocytes. However, the downstream protein target(s) that link UV radiation to the activation of signaling pathways responsible for cytokine expression have not been fully elucidated. In this study, we report a novel role of transglutaminase 2 (TG2), a member of the TG enzyme family whose activities are critical for cornified envelope formation, in mediating UV-induced inflammation. Our results showed that TG2-deficient mice exhibited reduced inflammatory responses to UV irradiation, including reduced erythema, edema, dilation of blood vessels, inflammatory cell infiltration, and levels of inflammatory cytokines. Using primary mouse keratinocytes and HaCaT cells, we found that UV irradiation-induced cytokine production by activating TG2, but not by upregulating TG2 expression, and that ER calcium release triggered by the UV-induced activation of phospholipase C was required for TG2 activation. Moreover, TG2 activity enhanced p65 phosphorylation, leading to an increase in NF-kappa B transcriptional activity. These results indicate that TG2 is a critical mediator of cytokine expression in the UV-induced inflammatory response of keratinocytes, and suggest that TG2 inhibition might be useful for preventing UV-related skin disorders, such as photoaging and skin cancer caused by chronic UV exposure.
provenance
Made available in Cube on 2018-09-28T16:07:52Z (GMT). No. of bitstreams: 0
language
English
author
Lee, Seok-Jin
Lee, Ki Baek
Son, Young Hoon
Shin, Jiwoong
Lee, Jin-Haeng
Kim, Hyo-Jun
Hong, Ah-Young
Bae, Hee Won
Kwon, Mee-ae
Lee, Won Jong
Kim, Jin-Hee
Lee, Dong Hun
Jeong, Eui Man
Kim, In-Gyu
orcid
Jeong, Eui Man/0000-0003-0692-2033
accessioned
2018-09-28T16:07:52Z
available
2018-09-28T16:07:52Z
issued
2017
citation
CELL DEATH & DISEASE(8)
issn
2041-4889
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/486447.do
Funder
보건복지부
Funding Program
첨단의료기술개발
Project ID
1465024470
Jurisdiction
Rep.of Korea
Project Name
Development of real-time assay method for live cell anti-oxidant capacity for monitoring and improving the quality of therapeutic stem cells
rights
openAccess
type
article


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