Introduction: The lacrimal gland (LG) of the CD25-/- model of Sjögren's syndrome (SS) has high interleukin (IL)-17, IL-13 and interferon-gamma (IFN-γ) cytokines. The specific contribution of these cytokines to the onset and severity of dacryoadenitis in the CD25-/- mice has not been evaluated.
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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4392623 | PMC |
| http://dx.doi.org/10.1186/s13075-015-0582-9 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Changes in tear cytokine and lactoferrin levels in postmenopausal women with primary acquired nasolacrimal duct obstruction complicated with obstructed meibomian gland dysfunction.
BMC Ophthalmol
January 2025
Department of Ophthalmology, Wuhu Eye Hospital, 378 Santan Road, Yijiang District, Anhui Province, Wuhu, 241002, China.
Background: Epiphora and secondary ocular surface damage are increasingly impairing the quality of life of people, particularly elderly women. We aimed to investigate the changes in tear cytokine and lactoferrin levels in postmenopausal women with primary acquired nasolacrimal duct obstruction (PANDO) complicated with obstructed meibomian gland dysfunction (OMGD) and preliminary explore the pathological mechanisms of OMGD in patients with PANDO.
Methods: The prospective study involved 43 and 41 postmenopausal women with and without PANDO, respectively.
Trophoblast-derived factors drive human mesenchymal stem cell differentiation along an endothelial lineage: A model of early placental vasculogenesis.
Reprod Biol
January 2025
Department of Biology, Edge Hill University, L39 4QP, UK. Electronic address:
Mechanisms controlling the process and patterning of blood vessel development in the placenta remain largely unknown. The close physical proximity of early blood vessels observed in the placenta and the cytotrophoblast, as well as the reported production of vasculogenic growth factors by the latter, suggests that signalling between these two niches may be important. Here, we have developed an in vitro model to address the hypothesis that the cytotrophoblast, by the secretion of soluble factors, drives differentiation of resident sub-trophoblastic mesenchymal stem cells (MSCs) along a vascular lineage, thereby establishing feto-placental circulation.
View Article and Find Full Text PDFA Conjugate of an EGFR-Binding Peptide and Doxorubicin Shows Selective Toxicity to Triple-Negative Breast Cancer Cells.
ACS Med Chem Lett
January 2025
Chapman University School of Pharmacy, Irvine, California 92618, United States.
Selective targeting of cancer cells via overexpressed cell-surface receptors is a promising strategy to enhance chemotherapy efficacy and minimize off-target side effects. In this study, we designed peptide 31 (YHWYGYTPERVI) to target the overexpressed epidermal growth factor receptor (EGFR) in triple-negative breast cancer (TNBC) cells. Peptide 31 is internalized by TNBC cells through EGFR-mediated endocytosis and shares sequence and structural similarities with human EGF (hEGF), a natural EGFR ligand.
View Article and Find Full Text PDFCells under high confinement form highly polarized hydrostatic pressure-driven, stable leader blebs that enable efficient migration in low adhesion, environments. Here we investigated the basis of the polarized bleb morphology of metastatic melanoma cells migrating in non-adhesive confinement. Using high-resolution time-lapse imaging and specific molecular perturbations, we found that EGF signaling via PI3K stabilizes and maintains a polarized leader bleb.
View Article and Find Full Text PDFNanostructured lipid carriers for enhanced batimastat delivery across the blood-brain barrier: an in vitro study for glioblastoma treatment.
Drug Deliv Transl Res
January 2025
i3S - Instituto de Investigação e Inovação em Saúde, University of Porto, Rua Alfredo Allen 208, 4200-135, Porto, Portugal.
Glioblastoma presents a significant treatment challenge due to the blood-brain barrier (BBB) hindering drug delivery, and the overexpression of matrix metalloproteinases (MMPs), which promotes tumor invasiveness. This study introduces a novel nanostructured lipid carrier (NLC) system designed for the delivery of batimastat, an MMP inhibitor, across the BBB and into the glioblastoma microenvironment. The NLCs were functionalized with epidermal growth factor (EGF) and a transferrin receptor-targeting construct to enhance BBB penetration and entrapment within the tumor microenvironment.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!