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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.
Assuntos

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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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