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

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

doi:10.3892/etm.2021.10831

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

Authors:
- Eun Ji Yeo
- Min Jea Shin
- Hyeon Ji Yeo
- Yeon Joo Choi
- Eun Jeong Sohn
- Lee Re Lee
- Hyun Jung Kwon
- Hyun Ju Cha
- Sung Ho Lee
- Sunghou Lee
- Yeon Hee Yu
- Duk-Soo Kim
- Dae Won Kim
- Jinseu Park
- Kyu Hyung Han
- Won Sik Eum
- Soo Young Choi
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Affiliations: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon 24252, Republic of Korea, Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Gangneung‑Wonju National University, Gangneung, Gangwon 25457, Republic of Korea, Department of Green Chemical Engineering, Sangmyung University, Cheonan, Chungcheongnam 31066, Republic of Korea, Department of Anatomy and BK21 FOUR Project, College of Medicine, Soonchunhyang University, Cheonan, Chungcheongnam 31538, Republic of Korea
Published online on: October 1, 2021 https://doi.org/10.3892/etm.2021.10831
Article Number: 1395

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Abstract

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‑κB, MAPK and Akt. Additionally, Tat‑Trx1 markedly reduced the production of inducible nitric oxide synthase, cyclooxygenase‑2, IL‑1β, IL‑6 and TNF‑α 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.

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