Recombinant human thioredoxin suppresses lipopolysaccharide-induced bronchoalveolar neutrophil infiltration in rat.

Abstract

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.

• Authors: Shugo Ueda, Takayuki Nakamura, Akira Yamada, Akie Teratani, Nao Matsui, Suzuyo Furukawa, Yuma Hoshino, Makiko Narita, Junji Yodoi, Hajime Nakamura
• Journal: Life sciences (Life Sci) Vol. 79 Issue 12 Pg. 1170-7 (Aug 15 2006) ISSN: 0024-3205 [Print] Netherlands
• PMID: 16643955 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chemokines
• Cytokines
• Indicators and Reagents
• Lipopolysaccharides
• Recombinant Proteins
• Intercellular Adhesion Molecule-1
• Thioredoxins

Topics

• Animals
• Body Weight (drug effects, physiology)
• Bronchoalveolar Lavage Fluid (cytology)
• Chemokines (metabolism)
• Cytokines (metabolism)
• Enzyme-Linked Immunosorbent Assay
• HT29 Cells (transplantation)
• Humans
• Indicators and Reagents
• Injections, Intravenous
• Intercellular Adhesion Molecule-1 (metabolism)
• Lipopolysaccharides (antagonists & inhibitors, toxicity)
• Lung (pathology)
• Male
• Neoplasm Transplantation
• Neutrophil Infiltration (drug effects)
• Organ Size (drug effects, physiology)
• Oxidation-Reduction
• Rats
• Rats, Wistar
• Recombinant Proteins (administration & dosage, pharmacokinetics, pharmacology)
• Thioredoxins (administration & dosage, pharmacokinetics, pharmacology)
• Transplantation, Heterologous