Recombinant human thioredoxin-1 becomes oxidized in circulation and suppresses bleomycin-induced neutrophil recruitment in the rat airway.
Thioredoxin-1 (TRX) is a redox-active protein with anti-inflammatory effects. This study investigated the optimal delivery method and the mechanisms of recombinant human TRX (rhTRX) to suppress neutrophil recruitment in a rat bleomycin (BLM)-induced sustained acute lung injury model. In male Wister rats intratracheally administered with 0.125 mg/kg BLM, 8 mg/kg/day rhTRX was intravenously administered on days 3-6 using one of three protocols: daily bolus injection, 3 h daily infusion or continuous infusion for 96 h. Only the continuous-infusion of rhTRX significantly reduced the neutrophil infiltration compared with the other two methods. The BLM-induced down-regulation of L-selectin expression on circulating neutrophils was inhibited by rhTRX. Oxidized rhTRX showed a comparable effect with reduced rhTRX and rhTRX incubated with plasma or circulating in plasma was more than 99% oxidized. These results suggest that rhTRX becomes oxidized in circulation and continuous infusion of rhTRX suppresses neutrophil recruitment in the airway.
Nakamura
Takayuki
T
Thioredoxin Project, Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Sakyo-ku, Kyoto, Japan.
Hoshino
Yuma
Y
Yamada
Akira
A
Teratani
Akie
A
Furukawa
Suzuyo
S
Okuyama
Hiroaki
H
Ueda
Shugo
S
Wada
Hiromi
H
Yodoi
Junji
J
Nakamura
Hajime
H
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001761:Bleomycin / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation; D019041:L-Selectin / Q000096:biosynthesis; D008297:Male; D009504:Neutrophils / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010100:Oxygen / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000737:chemistry*; D013879:Thioredoxins / Q000097:blood / Q000737:chemistry*; D014132:Trachea / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D011994:Recombinant Proteins; D001761:Bleomycin; D019041:L-Selectin; D013879:Thioredoxins; D010100:Oxygen