Aberrant IGF1-PI3K/AKT/MTOR signaling pathway regulates the local immunity of oral lichen planus.
Immunobiology
; 224(3): 455-461, 2019 05.
Article
in En
| MEDLINE
| ID: mdl-30773287
ABSTRACT
OBJECTIVES:
Oral lichen planus (OLP) is a T cell-mediated immune-related chronic disease, featured by accumulation of T cells and apoptosis of keratinocytes. Insulin-like growth factors 1 (IGF1) signaling, in combination with its downstream PI3K/AKT/MTOR cascade, plays pivotal roles in the regulation of inflammation and immune response. Meanwhile, TRB3 acts as a connective protein in the pathway. This study investigated the possible function of IGF1-PI3K/AKT/MTOR pathway in the local immunity of OLP.METHODS:
The expression of phosphorylated IGF1R (p-IGF1R) and TRB3 in lesional tissues of OLP was measured. The effects of T cells pretreated with PI3K inhibitor LY294002, MTOR antagonist rapamycin and exogenous IGF1 on the cell proliferation and apoptosis, as well as supernatant inflammatory cytokine levels were detected in co-culture system of activated T cells and oral keratinocytes, respectively.RESULTS:
The expression of p-IGF1R and TRB3 in OLP lesions was significantly increased when compared with controls (P < 0.001). Rapamycin-treated T cells displayed enhanced apoptosis rate and promoted proliferation of their keratinocytes in the co-culture system. Notably, abnormal expression of IFN-γ and IL-4 were detected in supernatant of T cell alone and co-culture system in response to pharmacological modulators of IGF1-PI3K/MTOR pathway.CONCLUSIONS:
The aberrant IGF1-PI3K/AKT/MTOR signaling may participate in the immunoregulatory mechanism of OLP, via regulation on the crosstalk between T cells and keratinocytes, as well as imbalanced cytokine networks.Key words
Full text:
1
Database:
MEDLINE
Main subject:
Repressor Proteins
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Insulin-Like Growth Factor I
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T-Lymphocytes
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Keratinocytes
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Protein Serine-Threonine Kinases
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Lichen Planus, Oral
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Cell Cycle Proteins
Limits:
Adult
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Female
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Humans
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Male
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Middle aged
Language:
En
Journal:
Immunobiology
Year:
2019
Type:
Article