Thioredoxin suppresses the contact hypersensitivity response by inhibiting leukocyte recruitment during the elicitation phase.
Thioredoxin, a redox-regulating protein that scavenges reactive oxygen species, appears to show an excellent antiinflammatory effect in treating animal models of various human inflammatory diseases. The aim of this study was to clarify whether thioredoxin is useful for treating inflammatory skin diseases, such as contact dermatitis, caused by epicutaneous exposure to environmental and occupational antigens. The allergic contact hypersensitivity response was suppressed in thioredoxin-transgenic mice. This suppressive effect of thioredoxin appeared to be via the inhibition of the efferent limb of contact hypersensitivity because administration of recombinant thioredoxin suppressed the inflammatory response in the elicitation phase but not in the induction phase. Adoptive-transfer studies revealed that the host environment, but not donor leukocytes, is critical in this suppressive effect. In thioredoxin-transgenic mice, the infiltration of neutrophils in the elicitation site was diminished, whereas the migratory function of cutaneous dendritic cells and hapten-specific cell proliferation were not disturbed. Thioredoxin-transgenic mice had also an attenuated inflammatory response to croton oil. These findings suggest that thioredoxin prevents skin inflammatory responses and could be a suitable candidate for the treatment of contact dermatitis.
Fukunaga
Atsushi
A
Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, Kobe, Japan. atsushi@med.kobe-u.ac.jp
Horikawa
Tatsuya
T
Ogura
Kanako
K
Taguchi
Kumiko
K
Yu
Xijun
X
Funasaka
Yoko
Y
Takeda
Masafumi
M
Nakamura
Hajime
H
Yodoi
Junji
J
Nishigori
Chikako
C
D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology; D017449:Dermatitis, Allergic Contact / Q000188:drug therapy / Q000276:immunology / Q000628:therapy; D004797:Enzyme-Linked Immunosorbent Assay; D000078404:Epidermal Cells; D005260:Female; D066298:In Vitro Techniques; D007962:Leukocytes / Q000166:cytology* / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D013879:Thioredoxins / Q000494:pharmacology*
D011994:Recombinant Proteins; D013879:Thioredoxins