Tat‑thioredoxin 1 reduces inflammation by inhibiting pro‑inflammatory cytokines and modulating MAPK signaling

• Published in: Experimental and therapeutic medicine 2021-12, Vol.22 (6), Article 1395
• Main Authors: Yeo, Eun Ji, Shin, Min Jea, Yeo, Hyeon Ji, Choi, Yeon Joo, Sohn, Eun Jeong, Lee, Lee Re, Kwon, Hyun Jung, Cha, Hyun Ju, Lee, Sung Ho, Lee, Sunghou, Yu, Yeon Hee, Kim, Duk-soo, Kim, Dae Won, Park, Jinseu, Han, Kyu Hyung, Eum, Won Sik, Choi, Soo Young
• Format: Article
• Language: English
• Subjects: Care and treatment; Cellular signal transduction; Cytokines; Development and progression; Health aspects; Inflammation; Mitogen-activated protein kinases; Physiological aspects; Thioredoxin
• ISSN: 1792-0981; 1792-1015
• DOI: 10.3892/etm.2021.10831

Thioredoxin 1 (Trx1) serves a central role in redox homeostasis. It is involved in numerous other processes, including oxidative stress and apoptosis. However, to the best of our knowledge, the role of Trx1 in inflammation remains to be explored. The present study investigated the function and mechanism of cell permeable fused Tat-Trx1 protein in macrophages and a mouse model. Transduction levels of Tat-Trx1 were determined via western blotting. Cellular distribution of transduced Tat-Trx1 was determined by fluorescence microscopy. 2',7'-Dichlorofluorescein diacetate and TUNEL staining were performed to determine the production of reactive oxygen species and DNA fragmentation. Protein and gene expression were measured by western blotting and reverse transcription-quantitative PCR (RT-qPCR), respectively. Effects of skin inflammation were determined using hematoxylin and eosin staining, changes in ear weight and ear thickness, and RT-qPCR in ear edema animal models. Transduced Tat-Trx1 inhibited lipopolysaccharide-induced cytotoxicity and activation of NF-[kappa]B, MAPK and Akt. Additionally, Tat-Trx1 markedly reduced the production of inducible nitric oxide synthase, cyclooxygenase-2, IL-1[beta], IL-6 and TNF-[alpha] in macrophages. In a 12-O-tetradecanoylphorbol-13-acetate-induced mouse model, Tat-Trx1 reduced inflammatory damage by inhibiting inflammatory mediator and cytokine production. Collectively, these results demonstrated that Tat-Trx1 could exert anti-inflammatory effects by inhibiting the production of pro-inflammatory mediators and cytokines and by modulating MAPK signaling. Therefore, Tat-Trx1 may be a useful therapeutic agent for diseases induced by inflammatory damage. Key words: Tat-thioredoxin 1, inflammation, MAPK, cytokines, protein therapy