Abstract | INTRODUCTION: METHODS: CD25-/-IL-17A-/-, CD25-/-IL-17-/-IFN-γ-/- and CD25-/-IFN-γ-/- were used at 4, 8, 12, 16 weeks (W). Total lymphocytic infiltration was evaluated by histology and characterized by flow cytometry. Epidermal growth factor ( EGF) concentration was measured in tears. Immunofluorescent staining evaluated expression of IFN-γ receptor (IFN-γR) and apoptosis. Real-time PCR evaluated inflammatory and T cell-related cytokines expression in LG. Caspase-3, -8, -9 activities was assayed in LG lysates. T helper cytokines were measured in serum by Luminex assay. RESULTS: The greatest total LG infiltration at 8 W was seen in CD25-/-IL-17A-/- (95%), followed by CD25-/- (71%) and IL-17-/- (12%). Tear EGF concentration was in normal range in CD25-/- at 4 W and in very low levels in both CD25-/- and CD25-/-IL-17A-/-. CD25-/- had high levels of inflammatory cytokines transcripts in LG compared to IL-17-/- mice; however, CD25-/-IL-17A-/- had even higher IL-1β, IFN-γR, caspase-3, -8, -9 mRNA levels, greater immunoreactivity to IFN-γR in LG acini, greater number of apoptotic+ cells and greater caspases activities in the LG at 8 W. CD25-/-IL-17A-/- had lower IL-13 concentration and lower IL-13/IFN-γ ratio compared to CD25-/- in serum. CD25-/-IFN-γ-/- had lower number of apoptotic+ cells and decreased caspase-3 expression in LG. CD25-/-IL-17-/-IFN-γ-/- had lower total lymphocytic cell infiltration at 8 W (48%), CD4+T cell infiltration and expression of IFN-γR and apoptotic+ cells in the LG and increased tear EGF concentration in tears. CONCLUSIONS: IFN-γ is critical for LG destruction and secretory dysfunction in the CD25-/- model of SS. Altered balance between IFN-γ and IL-13 in the CD25-/-IL-17A-/- mice accelerates LG destruction by increasing glandular apoptosis and facilitating apoptosis through increased expression of IFN-γR by glandular epithelium and activation of caspases. Targeting both IFN-γ and IL-17 may be beneficial for treating the LG inflammation in SS.
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Authors | Fang Bian, Flavia L Barbosa, Rosa M Corrales, Flavia S A Pelegrino, Eugene A Volpe, Stephen C Pflugfelder, Cintia S de Paiva |
Journal | Arthritis research & therapy
(Arthritis Res Ther)
Vol. 17
Pg. 53
(Mar 10 2015)
ISSN: 1478-6362 [Electronic] England |
PMID | 25889094
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Il2ra protein, mouse
- Interleukin-13
- Interleukin-2 Receptor alpha Subunit
- Interferon-gamma
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Topics |
- Animals
- Disease Models, Animal
- Enzyme-Linked Immunosorbent Assay
- Female
- Flow Cytometry
- Immunohistochemistry
- Interferon-gamma
(metabolism)
- Interleukin-13
(metabolism)
- Interleukin-2 Receptor alpha Subunit
(genetics)
- Lacrimal Apparatus
(metabolism, pathology)
- Male
- Mice
- Mice, Knockout
- Sjogren's Syndrome
(metabolism, pathology)
- Tears
(chemistry, metabolism)
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