Fluvastatin inhibits expression of the chemokine MDC/CCL22 induced by interferon-gamma in HaCaT cells, a human keratinocyte cell line.

Abstract

BACKGROUND AND PURPOSE:

The macrophage-derived chemokine (MDC/CCL22) is a prototypic Th2-type chemokine intimately involved in Th2-skewed allergic diseases, such as atopic dermatitis and asthma. The statins (3-hydroxy-3-methyl glutaryl coenzyme A reductase inhibitors) have been demonstrated to relieve allergic inflammation. However, the immunological effects and mechanisms of statins against atopic dermatitis remain unknown, at least in vitro. This study aimed to define how different statins affect MDC expression in HaCaT cells, a human keratinocyte cell line.

EXPERIMENTAL APPROACH:

To measure the effects of statins on MDC expression in HaCaT cells, we used a cell viability assay, reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay and Western blotting analyses.

KEY RESULTS:

Fluvastatin, but not atorvastatin or simvastatin, inhibited MDC expression induced by interferon (IFN)-gamma and NF-kappaB activation. A NF-kappaB inhibitor, but not a STAT1 inhibitor, suppressed MDC expression in HaCaT cells. Further, inhibition of p38 mitogen-activated protein kinases (MAPKs) significantly suppressed IFN-gamma-induced MDC expression and NF-kappaB activation. Interestingly, fluvastatin suppressed IFN-gamma-induced NF-kappaB activation in parallel with p38 MAPK phosphorylation.

CONCLUSIONS AND IMPLICATIONS:

These results indicate that fluvastatin inhibited expression of the CC chemokine MDC induced by IFN-gamma in HaCaT cells, by inhibiting NF-kappaB activation via the p38 MAPK pathway. This blockade of a Th2 chemokine by fluvastatin may suppress the infiltration of Th2 cells into skin lesions and lessen the skin inflammation seen in atopic dermatitis, suggesting a potential therapeutic use of fluvastatin for this condition.

• Authors: Xu-Feng Qi, Dong-Heui Kim, Yang-Suk Yoon, Jian-Hong Li, Dan Jin, Yung-Chien Teng, Soo-Ki Kim, Kyu-Jae Lee
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 157 Issue 8 Pg. 1441-50 (Aug 2009) ISSN: 1476-5381 [Electronic] England
• PMID: 19594754 (Publication Type: Journal Article)

Chemical References

• Chemokine CCL22
• Fatty Acids, Monounsaturated
• Heptanoic Acids
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Indoles
• NF-kappa B
• Pyrroles
• Fluvastatin
• Interferon-gamma
• Atorvastatin
• Simvastatin
• p38 Mitogen-Activated Protein Kinases

Topics

• Atorvastatin
• Cell Line
• Chemokine CCL22 (antagonists & inhibitors, biosynthesis)
• Fatty Acids, Monounsaturated (pharmacology)
• Fluvastatin
• Heptanoic Acids (pharmacology)
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (pharmacology)
• Indoles (pharmacology)
• Interferon-gamma (pharmacology)
• Keratinocytes (metabolism)
• NF-kappa B (agonists, metabolism)
• Pyrroles (pharmacology)
• Signal Transduction
• Simvastatin (pharmacology)
• Th2 Cells (metabolism)
• p38 Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)