Thioredoxin-interacting protein-derived peptide (TN13) inhibits LPS-induced inflammation by inhibiting p38 MAPK signaling.
Biochem Biophys Res Commun
; 507(1-4): 489-495, 2018 12 09.
Article
in En
| MEDLINE
| ID: mdl-30448175
ABSTRACT
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 264.7â¯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 264.7â¯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-1ß (IL-1ß), interleukin-6 (IL-6), nitric oxide (NO), inducible NO synthase (iNOS), and cyclooxygenase 2 (COX-2) in RAW 264.7â¯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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Peptides
/
MAP Kinase Signaling System
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P38 Mitogen-Activated Protein Kinases
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Inflammation
Limits:
Animals
Language:
En
Journal:
Biochem Biophys Res Commun
Year:
2018
Document type:
Article