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


METHODS
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.


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
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.
Qi
Xu-Feng
XF
Department of Environmental Medical Biology, Wonju College of Medicine, Yonsei University, Wonju, Gangwon, Korea.
Kim
Dong-Heui
DH
Yoon
Yang-Suk
YS
Li
Jian-Hong
JH
Jin
Dan
D
Teng
Yung-Chien
YC
Kim
Soo-Ki
SK
Lee
Kyu-Jae
KJ
D000069059:Atorvastatin; D002460:Cell Line; D054422:Chemokine CCL22 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D000077340:Fluvastatin; D006538:Heptanoic Acids / Q000494:pharmacology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D015603:Keratinocytes / Q000378:metabolism*; D016328:NF-kappa B / Q000819:agonists / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology; D015398:Signal Transduction; D019821:Simvastatin / Q000494:pharmacology; D018418:Th2 Cells / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D054422:Chemokine CCL22; D005229:Fatty Acids, Monounsaturated; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D016328:NF-kappa B; D011758:Pyrroles; D000077340:Fluvastatin; D007371:Interferon-gamma; D000069059:Atorvastatin; D019821:Simvastatin; D048051:p38 Mitogen-Activated Protein Kinases