Bacterial TIR domain-derived peptides inhibit innate immune signaling and catabolic responses in chondrocyte.
Animals
Bacteria
/ metabolism
Bacterial Outer Membrane Proteins
/ metabolism
Cell Line
Cells, Cultured
Chondrocytes
/ immunology
Cytokines
/ metabolism
Humans
Immunity, Innate
/ drug effects
Inflammation
/ metabolism
Interleukin-1beta
/ metabolism
Mice
NF-kappa B
/ metabolism
Osteoarthritis
/ immunology
Peptides
/ metabolism
Protein Domains
Receptors, Interleukin-1
/ metabolism
Signal Transduction
/ drug effects
Tumor Necrosis Factor-alpha
/ metabolism
Catabolic responses
Chondrocyte
Decoy peptide
Innate immune signaling
TLR pathway
Journal
Molecular biology reports
ISSN: 1573-4978
Titre abrégé: Mol Biol Rep
Pays: Netherlands
ID NLM: 0403234
Informations de publication
Date de publication:
Apr 2019
Apr 2019
Historique:
received:
06
09
2018
accepted:
19
01
2019
pubmed:
29
3
2019
medline:
26
7
2019
entrez:
29
3
2019
Statut:
ppublish
Résumé
Osteoarthritis (OA) is a degenerative joint disease, in which low-grade inflammation plays an important role at the initiating step. Low-doses of LPS-induced inflammation in the plasma activate chondrocytes and promote the secretion proinflammatory cytokines, leading to secondary inflammation. Blocking OA-associated TLR activation is a promising strategy for the development of suitable therapies. Here, we want to find some bacteria-derived peptides that can block TLR signaling in chondrocytes more efficiently. Based on previous studies, we screened 12 TIR domain-derived peptides for their effects on NF-кB activation induced by LPS, IL-1β or TNF-α in murine ATDC-5 cells. We evaluated their effects on LPS-induced cytokine expression and secretion. Among them, two bacteria-derived peptides, TcpC-DD and TcpB-DD, showed the most potent inhibitory activities. In comparison with TcpB-DD, TcpC-DD exhibited broader TLR-inhibitory specificity during inflammation in chondrocytes. Furthermore, both TcpC-DD and TcpB-DD displayed strong inhibition of LPS- and IL-1β-induced catabolic reactions in chondrocytes. However, only TcpC-DD exhibited obvious suppression of TNF-α-induced catabolism. In conclusion, we identified two novel inhibitory peptides that modulate catabolism in chondrocytes and innate immune responses, and these peptides could be used to develop novel therapeutic strategies for OA.
Identifiants
pubmed: 30919211
doi: 10.1007/s11033-019-04627-8
pii: 10.1007/s11033-019-04627-8
doi:
Substances chimiques
Bacterial Outer Membrane Proteins
0
Cytokines
0
Interleukin-1beta
0
NF-kappa B
0
Peptides
0
Receptors, Interleukin-1
0
TLR protein, bacteria
0
Tumor Necrosis Factor-alpha
0
Types de publication
Journal Article
Langues
eng
Pagination
2493-2504Subventions
Organisme : National Key Research and Development Program of China
ID : 2016YFC1202905
Organisme : National Key Research and Development Program of China
ID : 2017ZX10103003
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