Upregulation of IL-6 expression in human salivary gland cell line by IL-17 via activation of p38 MAPK, ERK, PI3K/Akt, and NF-κB pathways.
J Oral Pathol Med
; 47(9): 847-855, 2018 Oct.
Article
em En
| MEDLINE
| ID: mdl-30007092
ABSTRACT
BACKGROUND:
The human salivary gland (HSG) cell line has so far been used as in vitro models for study of the influence of cytokines and pharmacologic agents on salivary glands, as well as a model system for inflammation in Sjögren's syndrome (SS). This study aimed to determine the effect of IL-17 on IL-6 production and the underlying molecular mechanism regulated by the HSG cell line.METHODS:
Immunofluorescence analyses, RT-PCR, and Western blot were conducted to evaluate the IL-17 receptor (IL-17R) expression in cultured HSG cells. Real-time PCR and ELISA were then utilized to establish the mRNA and protein levels of IL-6 in IL-17-stimulated HSG cells. Western blot, flow cytometry, immunofluorescence, and inhibitor analyses were conducted to elucidate the involved signaling pathways.RESULTS:
The HSG cells reliably expressed the IL-17R mRNA and its encoded surface-bound protein. The expression of IL-6 mRNA and protein was upregulated by stimulation of HSG cells with IL-17; this effect was impeded by IL-17- or IL-17R-neutralizing antibodies. IL-17 stimulation ended up with the fast phosphorylation of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), Akt, and translocation of nuclear factor-kappaB (NF-κB) in the HSG cells. p38 MAPK, Akt, and NF-κB inhibitors significantly subdued IL-6 generation in HSG cells stimulated by IL-17. PD98059, an ERK inhibitor, decreased IL-6 generation under low dose of IL-17 but not with high dose.CONCLUSIONS:
The HSG cells expressed IL-17R and reacted to IL-17 to generate IL-6 via the stimulation of ERK, p38 MAPK, Akt, and NF-κB signaling pathways.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glândulas Salivares
/
Síndrome de Sjogren
/
Expressão Gênica
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Regulação para Cima
/
NF-kappa B
/
Interleucina-6
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Fosfatidilinositol 3-Quinases
/
Interleucina-17
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MAP Quinases Reguladas por Sinal Extracelular
/
Proteínas Proto-Oncogênicas c-akt
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article