Suppressive effect of recombinant human thioredoxin on ultraviolet light-induced inflammation and apoptosis in murine skin.

Abstract

Thioredoxin (TRX) is a small ubiquitous protein, which regulates cellular redox status and scavenges reactive oxygen species. The present study was conducted to investigate the effect of TRX on ultraviolet (UV)-B-mediated inflammatory and apoptotic responses. Ear swelling after UV-B irradiation was significantly reduced in TRX-transgenic mice compared to wild-type mice. Administration i.p. of recombinant human TRX also reduced acute skin inflammatory reaction, such as skin erythema and swelling. Histologically, numbers of inflammatory cells including neutrophils and lymphocytes were significantly reduced and the average size of the caliber of blood vessels were also reduced in recombinant human TRX-injected mice. The number of apoptotic keratinocytes, in terms of sunburn cells, activated-caspase-3-positive cells and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells were all significantly reduced in recombinant human TRX-injected mice. Immunohistochemical intensity of 8-hydroxy-2'-deoxyguanosine was strikingly reduced in recombinant human TRX-injected mouse. Western blotting showed that administration of recombinant human TRX attenuated duration of phosphorylation of p38 mitogen-activated protein kinases and intensity of phosphorylation of c-Jun N-terminal kinase in the early phase, which play important roles in inflammatory and apoptotic signaling. Collectively, these findings indicated that recombinant human TRX attenuated inflammatory and apoptotic responses caused by UV-B. Possible mechanisms for this might be via redox regulation of stress signaling and reduction of reactive oxygen species.

• Authors: Ryusuke Ono, Taro Masaki, Siphora Dien, Xijun Yu, Atsushi Fukunaga, Junji Yodoi, Chikako Nishigori
• Journal: The Journal of dermatology (J Dermatol) Vol. 39 Issue 10 Pg. 843-51 (Oct 2012) ISSN: 1346-8138 [Electronic] England
• PMID: 22568890 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 Japanese Dermatological Association.

Chemical References

• Dermatologic Agents
• Recombinant Proteins
• TXN protein, human
• Thioredoxins

Topics

• Animals
• Apoptosis (drug effects)
• Dermatologic Agents (therapeutic use)
• Female
• Humans
• Keratinocytes (drug effects)
• Lymphocytes (drug effects)
• MAP Kinase Signaling System (drug effects)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Neutrophils (drug effects)
• Radiodermatitis (drug therapy, pathology)
• Recombinant Proteins (therapeutic use)
• Skin (drug effects, pathology, radiation effects)
• Sunburn (drug therapy, pathology)
• Thioredoxins (therapeutic use)
• Ultraviolet Rays (adverse effects)