title: Redox-active protein thioredoxin prevents proinflammatory cytokine- or bleomycin-induced lung injury.
abstract: Thioredoxin (TRX) is a multifunctional redox (reduction/oxidation)-active protein that scavenges reactive oxygen species by itself or together with TRX-dependent peroxiredoxin. TRX also has chemotaxis-modulating functions and suppresses leukocyte infiltration into sites of inflammation. Leukocyte infiltration and oxidative stress may be involved in the pathogenesis of several diseases, including interstitial lung diseases (ILD). We examined the effects of TRX in two mouse models of human ILD. Recently, we established a new mouse model for human ILD in which daily administration of proinflammatory cytokine interleukin (IL)-18 with IL-2 induces lethal lung injury accompanied by acute interstitial inflammatory responses. Administration of recombinant TRX suppressed IL-18/IL-2-induced interstitial infiltration of cells and prevented death and lung tissue damage. TRX-transgenic mice also showed resistance to lethal lung injury caused by IL-18/IL-2. Administration of bleomycin induces the infiltration of polymorphonuclear and mononuclear leukocytes in the pulmonary interstitium, followed by progressive fibrosis. Wild-type mice given recombinant TRX treatment and TRX-transgenic mice demonstrated a decrease in bleomycin-induced cellular infiltrates and fibrotic changes in the lung tissue. These results suggest that TRX modulates pulmonary inflammatory responses and acts to prevent lung injury. TRX may have clinical benefits in human ILD, including lung fibrosis, for which no effective therapeutic strategy currently exists.
authors.affiliation: Department of Internal Medicine 1, Kurume University, Kurume, Japan. hoshino@med.kurume-u.ac.jp
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Hoshino
authors.forename: Hajime
authors.initials: H
authors.lastname: Nakamura
authors.forename: Masaki
authors.initials: M
authors.lastname: Okamoto
authors.forename: Seiya
authors.initials: S
authors.lastname: Kato
authors.forename: Shinichi
authors.initials: S
authors.lastname: Araya
authors.forename: Keiko
authors.initials: K
authors.lastname: Nomiyama
authors.forename: Kotaro
authors.initials: K
authors.lastname: Oizumi
authors.forename: Howard A
authors.initials: HA
authors.lastname: Young
authors.forename: Hisamichi
authors.initials: H
authors.lastname: Aizawa
authors.forename: Junji
authors.initials: J
authors.lastname: Yodoi
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects; D001761:Bleomycin / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D020382:Interleukin-18 / Q000009:adverse effects / Q000037:antagonists & inhibitors* / Q000235:genetics; D007376:Interleukin-2 / Q000009:adverse effects / Q000037:antagonists & inhibitors* / Q000235:genetics; D017563:Lung Diseases, Interstitial / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013879:Thioredoxins / Q000494:pharmacology*
chemical_list: D000964:Antimetabolites, Antineoplastic; D018925:Chemokines; D020382:Interleukin-18; D007376:Interleukin-2; D001761:Bleomycin; D013879:Thioredoxins