Transglutaminase 2 mediates UV-induced skin inflammation by enhancing inflammatory cytokine production.

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-κB 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.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Lee SJ,Lee KB,Son YH,Shin J,Lee JH,Kim HJ,Hong AY,Bae HW,Kwon MA,Lee WJ,Kim JH,Lee DH,Jeong EM,Kim IG

doi

10.1038/cddis.2017.550

subject

Has Abstract

pub_date

2017-10-26 00:00:00

pages

e3148

issue

10

issn

2041-4889

pii

cddis2017550

journal_volume

8

pub_type

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