Thioredoxin-interacting protein-derived peptide (TN13) inhibits LPS-induced inflammation by inhibiting p38 MAPK signaling

Journal Article · Sat Dec 15 04:00:00 EST 2018 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2018.11.069· OSTI ID:23107886

Kim, Dong Oh ^[1]; Byun, Jae-Eun ^[1]; Seong, Hyun-A. ^[2]; Choi, Inpyo ^[1]; Jung, Haiyoung ^[1]

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1. Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yuseong-gu, Daejeon, 34141 (Korea, Republic of)
2. Department of Biochemistry, School of Life Sciences, Chungbuk National University, Cheongju, 28644 (Korea, Republic of)

Highlights: • TAT-TN13 suppresses p38 MAPK activity. • TAT-TN13 inhibits LPS-induced activation of macrophages. • TAT-TN13 downregulates NF-κB and AP-1 transcriptional activities. • TAT-TN13 inhibits LPS-induced inflammation in vitro and in vivo. Inflammation comprises an innate immune response, and is mainly induced by macrophages to protect the host from pathogens and mechanical injuries. The p38 mitogen-activated protein kinase (MAPK) pathway is a key regulator of inflammatory responses in macrophages. Here, we investigated the anti-inflammatory effects of thioredoxin-interacting protein-derived peptide (TN13) in macrophages in vitro and in vivo. Human immunodeficiency virus (HIV) trans-activator protein (TAT)-conjugated TN13 (TAT-TN13) was found to penetrate RAW 264.7 cells and decrease p38 MAPK activation in a dose-dependent manner. We also showed that TAT-TN13 could significantly inhibit lipopolysaccharide (LPS)-induced expression of macrophage activation-related receptors including CD80, CD86, and MHC II, as well as the transcriptional activation of nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1) in RAW 264.7 cells and primary mouse splenic macrophages. Furthermore, TAT-TN13 decreased the LPS-induced production of proinflammatory cytokines and mediators such as tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), nitric oxide (NO), inducible NO synthase (iNOS), and cyclooxygenase 2 (COX-2) in RAW 264.7 cells and mice. These results indicate that TAT-TN13 can inhibit macrophage-derived inflammation by inhibiting p38 MAPK activity and might represent a potential novel drug for the treatment of inflammation-related diseases.

• OSTI ID: 23107886
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1-4 Vol. 507; ISSN BBRCA9; ISSN 0006-291X
• Country of Publication: United States
• Language: English

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60 APPLIED LIFE SCIENCES
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NITRIC OXIDE
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