The immunomodulatory effects of barettin and involvement of the kinases CAMK1α and RIPK2.

Abstract

BACKGROUND:

Barettin is a marine natural compound with reported anti-inflammatory and antioxidant properties. The combination of these effects led us to explore barettin further as an inhibitor of atherosclerosis development.

METHODS:

The effect of barettin on MCP-1 and IL-10 secretion from activated immune cells was detected by ELISA. Determination of cell viability of oxidized low-density lipoprotein (oxLDL) and barettin exposed HUVEC cells were investigated by using CellTiter 96® AQ(ueous) One Solution. The kinase inhibition assays were performed using a radioactive ((33)P-ATP) filter binding assay at the University of Dundee, UK.

RESULTS:

Barettin reduces the secretion of monocyte chemotactic protein-1 (MCP-1) from LPS-stimulated monocytes, but was not able to prevent oxLDL-induced cell death in HUVEC. Barettin has inhibitory activity against two protein kinases related to inflammation, namely the receptor-interacting serine/threonine kinase 2 (RIPK2) and calcium/calmodulin-dependent protein kinase 1α (CAMK1α). We also demonstrate that barettin reduce the production of the anti-inflammatory cytokine interleukin-10 (IL-10) in a dose and time-dependent manner, possibly by inhibiting CAMK1α.

CONCLUSIONS:

The anti-inflammatory activity of barettin is exerted through the regulation of inflammatory mediators such as MCP-1 and IL-10, possibly via inhibition of kinases.

• Authors: Karianne Fredenfeldt Lind, Bjarne Østerud, Espen Hansen, Trond Ø Jørgensen, Jeanette Hammer Andersen
• Journal: Immunopharmacology and immunotoxicology (Immunopharmacol Immunotoxicol) Vol. 37 Issue 5 Pg. 458-64 ( 2015) ISSN: 1532-2513 [Electronic] England
• PMID: 26466644 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents
• CCL2 protein, human
• Chemokine CCL2
• IL10 protein, human
• Immunologic Factors
• Peptides, Cyclic
• Protein Kinase Inhibitors
• barettin
• Interleukin-10
• RIPK2 protein, human
• Receptor-Interacting Protein Serine-Threonine Kinase 2
• CAMK1 protein, human
• Calcium-Calmodulin-Dependent Protein Kinase Type 1

Topics

• Anti-Inflammatory Agents (pharmacology)
• Calcium-Calmodulin-Dependent Protein Kinase Type 1 (antagonists & inhibitors, immunology)
• Cell Line, Tumor
• Chemokine CCL2 (immunology)
• Human Umbilical Vein Endothelial Cells (cytology, immunology)
• Humans
• Immunologic Factors (pharmacology)
• Interleukin-10 (immunology)
• Peptides, Cyclic (pharmacology)
• Protein Kinase Inhibitors (pharmacology)
• Receptor-Interacting Protein Serine-Threonine Kinase 2 (antagonists & inhibitors, immunology)