Synergistic Inhibition of Tumor Necrosis Factor-Alpha-Stimulated Pro-Inflammatory Cytokine Expression in HaCaT Cells by a Combination of Rapamycin and Mycophenolic Acid
Annals of Dermatology
;
: 32-39, 2015.
Artigo
em Inglês
| WPRIM
| ID: wpr-11503
ABSTRACT
BACKGROUND:
Keratinocytes release various pro-inflammatory cytokines, chemokines, and adhesion molecules such as intercellular adhesion molecule 1 (ICAM-1) in response to cytokines such as tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma. Rapamycin and mycophenolic acid (MPA) have potent immunosuppressive activity because they inhibit lymphocyte proliferation.OBJECTIVE:
We investigated the effects of rapamycin and MPA on the expression of inflammation-related factors such as ICAM-1 and inducible nitric oxide synthase (iNOS), pro-inflammatory cytokines and chemokines, and related signaling pathways in TNF-alpha-stimulated HaCaT cells.METHODS:
The viability of HaCaT cells treated with rapamycin and MPA was confirmed using MTT assay. The expression of various cytokines such as interleukin (IL)-1beta, IL-6, and IL-8; inflammation-related factors such as ICAM-1 and iNOS; and the activation of mitogen activated protein kinase (MAPK) signaling pathways mediated by extracellular signal-related kinases (ERK), p38, and c-Jun N-terminal kinases (JNK) in TNF-alpha-stimulated HaCaT cells were confirmed using reverse transcription-polymerase chain reaction and western blotting.RESULTS:
Combined treatment of TNF-alpha-induced HaCaT cells with rapamycin and MPA decreased ICAM-1 and iNOS expression and ERK and p38 activation more than treatment with either drug alone. The most significant decrease was observed with a combination of rapamycin (80 nM) and MPA (20 nM). These results show that co-treatment with these agents has a synergistic anti-inflammatory effect by blocking the activation of the ERK/p38 MAPK signaling pathway and thus suppressing the TNF-alpha-induced expression of ICAM-1 and iNOS.CONCLUSION:
The combination of rapamycin and MPA could potentially be used as a therapeutic approach in inflammatory skin diseases.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Fosfotransferases
/
Proteínas Quinases
/
Dermatopatias
/
Linfócitos
/
Queratinócitos
/
Western Blotting
/
Citocinas
/
Interleucina-8
/
Interleucinas
/
Interferons
Idioma:
Inglês
Revista:
Annals of Dermatology
Ano de publicação:
2015
Tipo de documento:
Artigo
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