PEP-1-FK506BP12 inhibits matrix metalloproteinase expression in human articular chondrocytes and in a mouse carrageenan-induced arthritis model.

Abstract

The 12 kDa FK506-binding protein (FK506BP12), an immunosuppressor, modulates T cell activation via calcineurin inhibition. In this study, we investigated the ability of PEP-1-FK506BP12, consisting of FK506BP12 fused to the protein transduction domain PEP-1 peptide, to suppress catabolic responses in primary human chondrocytes and in a mouse carrageenan-induced paw arthritis model. Western blotting and immunofluorescence analysis showed that PEP-1-FK506BP12 efficiently penetrated chondrocytes and cartilage explants. In interleukin-1β (IL-1β)-treated chondrocytes, PEP-1-FK506BP12 significantly suppressed the expression of catabolic enzymes, including matrix metalloproteinases (MMPs)-1, -3, and -13 in addition to cyclooxygenase-2, at both the mRNA and protein levels, whereas FK506BP12 alone did not. In addition, PEP-1-FK506BP12 decreased IL-1β-induced phosphorylation of the mitogen-activated protein kinase (MAPK) complex (p38, JNK, and ERK) and the inhibitor kappa B alpha. In the mouse model of carrageenan-induced paw arthritis, PEP-1-FK506BP12 suppressed both carrageenan-induced MMP-13 production and paw inflammation. PEP-1-FK506BP12 may have therapeutic potential in the alleviation of OA progression.

• Authors: Hyun Sook Hwang, In Young Park, Dae Won Kim, Soo Young Choi, Young Ok Jung, Hyun Ah Kim
• Journal: BMB reports (BMB Rep) Vol. 48 Issue 7 Pg. 407-12 (Jul 2015) ISSN: 1976-670X [Electronic] Korea (South)
• PMID: 25887750 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-1beta
• NF-kappa B
• Pep-1 peptide
• Peptides
• Recombinant Fusion Proteins
• Cysteamine
• Carrageenan
• Mitogen-Activated Protein Kinases
• Matrix Metalloproteinase 13
• Tacrolimus Binding Protein 1A

Topics

• Animals
• Arthritis (chemically induced, complications, enzymology, pathology)
• Carrageenan
• Cartilage, Articular (pathology)
• Cells, Cultured
• Chondrocytes (drug effects, enzymology, pathology)
• Cysteamine (analogs & derivatives, pharmacology)
• Disease Models, Animal
• Edema (complications, drug therapy, pathology)
• Humans
• Interleukin-1beta (pharmacology)
• Matrix Metalloproteinase 13 (metabolism)
• Mice
• Mitogen-Activated Protein Kinases (metabolism)
• NF-kappa B (metabolism)
• Peptides (pharmacology)
• Recombinant Fusion Proteins (pharmacology, therapeutic use)
• Tacrolimus Binding Protein 1A (metabolism)
• Transduction, Genetic