Recombinant human thioredoxin suppresses lipopolysaccharide-induced bronchoalveolar neutrophil infiltration in rat.
Human thioredoxin (TRX) is a multifunctional redox-active protein. We previously reported that the intraperitoneal administration of recombinant human thioredoxin (rhTRX) attenuates inflammatory cytokine- or bleomycin-induced lung injury in mice. In this study, the effect of rhTRX injected intravenously after lipopolysaccharide (LPS) injection was analyzed in rats. Rats were injected with LPS followed by treatment with rhTRX. Although the bolus injection exerted no protective effect, continuous intravenous administration of rhTRX significantly suppressed percentage number of neutrophils in bronchoalveolar lavage fluid. Histological examination also showed that rhTRX decreased neutrophil infiltration in the lung tissues. Administered rhTRX was mainly excreted into the urine and the tissue accumulation of rhTRX in the lung was marginal. LPS-induced oxidative stress in the lung was slight in this model. These results demonstrated that continuous intravenous administration of rhTRX suppresses LPS-induced bronchoalveolar neutrophil infiltration by an anti-chemotactic effect. Administration of rhTRX did not promote the tumor growth nor affect chemosensitivity in the xenotransplantation model, suggesting the safety of rhTRX therapy for cancer patients.
Ueda
Shugo
S
Thioredoxin Project, Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Kyoto, 606-8507, Japan.
Nakamura
Takayuki
T
Yamada
Akira
A
Teratani
Akie
A
Matsui
Nao
N
Furukawa
Suzuyo
S
Hoshino
Yuma
Y
Narita
Makiko
M
Yodoi
Junji
J
Nakamura
Hajime
H
D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D019073:HT29 Cells / Q000637:transplantation; D006801:Humans; D007202:Indicators and Reagents; D007275:Injections, Intravenous; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000633:toxicity; D008168:Lung / Q000473:pathology; D008297:Male; D009368:Neoplasm Transplantation; D020556:Neutrophil Infiltration / Q000187:drug effects*; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D013879:Thioredoxins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D014183:Transplantation, Heterologous
D018925:Chemokines; D016207:Cytokines; D007202:Indicators and Reagents; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1; D013879:Thioredoxins