Enhancement of keratinocyte survival and migration elicited by interleukin 24 upregulation in dermal microvascular endothelium upon welding-fume exposure

ABSTRACT

Occupational exposure to welding fumes constitutes a serious health concern. Although the effects of fumes on the respiratory tract have been investigated, few apparent reports were published on their effects on the skin. The purpose of this study was to investigate the effects of exposure to welding fumes on skin cells, focusing on interleukin-24 (IL-24), a cytokine involved in the pathophysiology of skin conditions, such as atopic dermatitis and psoriasis. Treatment with welding fumes increased IL-24 expression and production levels in human dermal microvascular endothelial cells (HDMEC) which were higher than that in normal human epidermal keratinocytes. IL-24 levels in Trolox and deferoxamine markedly suppressed welding fume-induced IL-24 expression in HDMEC, indicating that oxidative stress may be involved in this cytokine expression. IL-24 released from HDMEC protected keratinocytes from welding fume-induced damage and enhanced keratinocyte migration. Serum IL-24 was higher in welding workers than in general subjects and was positively correlated with elevated serum levels of 8-hydroxy-2’-deoxyguanosine, an oxidative stress marker. In summary, welding fumes enhanced IL-24 expression in HDMEC, stimulating keratinocyte survival and migration. IL-24 expression in endothelial cells may act as an adaptive response to welding-fume exposure in the skin.

KEYWORDS:

• Welding fumes
• IL-24
• endothelial cells
• keratinocytes
• oxidative stress

Acknowledgments

The authors thank Dr. Miki Tanaka and Mr. Shinji Kawano for their technical assistance during this study.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

All data generated or analyzed in this study are included in this published article.

Author contributions

Conceptualization, MaK and YI; methodology, MaK, MT and YI; investigation, MaK, NI, YN, TO, MH, CK, CFAV, MT and YI; visualization, MaK and YI; funding acquisition, MT and YI; project administration, CFAV, MT and YI; writing – original draft, MaK, TN, MiK and YI; writing – review and editing, all authors. All authors have read and agreed to the published version of the manuscript.

Additional information

Funding

This work was supported by KAKENHI grants from the Japan Society for the Promotion of Science (grant numbers [20H04341] and [17H04714] to YI), Environment Research and Technology Development Funds of the Environmental Restoration and Conservation Agency of Japan (grant numbers [JPMEERF20215003 and JPMEERF20205007] to YI), and the MHLW Program (grant number [JPMH200501] to MT).