Dysregulated co-stimulatory molecule expression in a Sjögren’s syndrome mouse model with potential implications by microRNA-146a

Gauna, Adrienne E.; Park, Yun‐Jong; Nayar, Gautam; Onate, Marelys; Stewart, Carol M.; Yu, Qing; Cha, Seunghee

doi:10.1016/j.molimm.2015.09.027

Cited by 11 publications

(4 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…B-lymphocyte derived cytokines, including IL-2, IL-4, IL6, IL10 and IFN-γ are likely to serve as effectors [ 16 , 21 , 22 ]. B lymphocytes act as antigen-presenting cells [ 40 – 42 ], behave as autophagic cells to bridge the gap between innate and adaptive responses, and regulate the formation of germinal centers via the production of lymphotoxins.…”

Section: Discussionmentioning

confidence: 99%

Leptin/OB-R pathway promotes IL-4 secretion from B lymphocytes and induces salivary gland epithelial cell apoptosis in Sjögren's syndrome

Xie

et al. 2017

Oncotarget

View full text Add to dashboard Cite

Sjögren's syndrome (SjS) is a chronic autoimmune epithelitis in which cell apoptosis promotes the formation of inflammatory lesions. We used immunohistochemistry and TUNEL to assay B cell infiltration and apoptosis in salivary gland tissue from 16-week-old NOD/LtJ mice with SjS. In co-cultures of primary salivary glandepithelial cells (SGECs) and spleen B cells, we assessed SGEC viability and apoptosis using CCK8 assays and flow cytometry. ELISAs were employed to assess cytokine levels in culture medium. Leptin protein, leptin receptor (OB-R), pro- and anti-apoptotic proteins, and Jak2/Stat3/ERK signaling molecules were analyzed using western blotting. B cell infiltration and salivary gland apoptosis were increased in salivary tissue from mice with SjS. Leptin treatment had no effect on cell viability or apoptosis among B cells and primary SGECs. B cell and SGEC co-culture systems showed that leptin increased apoptosis induced by B lymphocytes, reduced SGEC cell viability, and promoted IL-4 secretion from B cells. This suggests Leptin/OB-R signaling stimulates B cells-induced SGEC apoptosis via IL-4 secretion and OB-R-Jak2-Stat3 activation.

show abstract

Section: Discussionmentioning

confidence: 99%

Leptin/OB-R pathway promotes IL-4 secretion from B lymphocytes and induces salivary gland epithelial cell apoptosis in Sjögren's syndrome

Xie

et al. 2017

Oncotarget

View full text Add to dashboard Cite

show abstract

“…Exosomes are measured in nanometers, so they have a quantitative advantage. In addition, miR-146a-5p can inhibit the transfer of kidney clear cell carcinoma [ 41 ], improve allergic rhinitis [ 42 ], promote chondrocyte phagocytosi [ 43 ], enhance differentiation of spermatogonia [ 44 ] and delay senile dementia [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Analysis of differentially expressed microRNA of TNF-α-stimulated mesenchymal stem cells and exosomes from their culture supernatant

Ma¹,

Zhang²,

Xü³

et al. 2018

aoms

View full text Add to dashboard Cite

IntroductionTo analyze the microRNA expression of tumor necrosi factor α (TNF-α) stimulated mesenchymal stem cells (MSCs) and exosomes from their culture supernatant.Material and methodsTNF-α (20 ng/ml) was used to stimulate MSCs, which were then regarded as TNF-α cells (TC), while unstimulated cells were the normal control cells (NCC). MSCs and their culture supernatant were harvested after 48 h. Subsequently, exosomes were isolated from culture supernatants with ExoQuick-TC and were divided into two groups, TNF-α exosomes (TE) and normal control exosomes (NCE). Then, the microRNAs were measured by high-throughput sequencing and the results were differentially analyzed. Finally, the correlation of the target genes corresponding to differently expressed microRNAs was analyzed by gene ontology (GO) and KEGG pathway analysis.ResultsHigh-throughput sequencing showed that the cellular compartment (TC vs. NCC) had 280 microRNAs. miR-146a-5p was a uniquely up-regulated microRNA (p < 0.001) and the most significantly down-regulated microRNA among the 279 microRNAs included was miR-150-5p (p < 0.001). There were 180 differentially expressed microRNAs in the exosome compartment (TE vs. NCE), where miR-146-5p (p < 0.001) was one of 176 upregulated microRNAs and miR-203b-5p (p < 0.001) was one of 4 downregulated microRNAs. Coincidentally, bioinformatics analysis showed that IRAK1 was a critical target gene of miR-146-5p related to the Toll-like receptor (TLR) signaling pathway.ConclusionsIn contrast with the control group, there were significantly differentially expressed microRNAs in both MSCs and exosomes. Interestingly, miR-146a-5p was up-regulated in both comparative groups, and its target gene IRAK1 plays a crucial part in the TLR signaling pathway. These investigations demonstrate a new direction for subsequent inflammation mechanistic studies.

show abstract

“…In an SS-susceptible mouse model, miR-146a expression was shown upregulated in the SGs at both 8 weeks (early phase of disease) and 20 weeks (late phase of disease) of age [ 65 ]. Further studies indicate that co-stimulatory molecule CD80 in SGECs is a potential target directly inhibited by miR-146a, thus altering CD86: CD80 ratio [ 66 ]. Moreover, miR-1248 [ 67 ] exerts its functions on SOCE, which will be discussed and illustrated in “ The defect of calcium signaling ” section and Fig.…”

Section: Epigenetic Dysregulation In Sgecsmentioning

confidence: 99%

Primary Sjögren’s syndrome: new perspectives on salivary gland epithelial cells

Hou,

Feng,

Yang

et al. 2024

Eur J Med Res

View full text Add to dashboard Cite

Primary Sjögren’s syndrome (pSS) is a chronic autoimmune disease primarily affecting exocrine glands such as the salivary glands, leading to impaired secretion and sicca symptoms. As the mainstay of salivation, salivary gland epithelial cells (SGECs) have an important role in the pathology of pSS. Emerging evidence suggests that the interplay between immunological factors and SGECs may not be the initial trigger or the sole mechanism responsible for xerostomia in pSS, challenging conventional perceptions. To deepen our understanding, current research regarding SGECs in pSS was reviewed. Among the extensive aberrations in cellular architecture and function, this review highlighted certain alterations of SGECs that were identified to occur independently of or in absence of lymphocytic infiltration. In particular, some of these alterations may serve as upstream factors of immuno-inflammatory responses. These findings underscore the significance of introspecting the pathogenesis of pSS and developing interventions targeting SGECs in the early stages of the disease. Graphical Abstract

show abstract

Dysregulated co-stimulatory molecule expression in a Sjögren’s syndrome mouse model with potential implications by microRNA-146a

Cited by 11 publications

References 43 publications

Leptin/OB-R pathway promotes IL-4 secretion from B lymphocytes and induces salivary gland epithelial cell apoptosis in Sjögren's syndrome

Leptin/OB-R pathway promotes IL-4 secretion from B lymphocytes and induces salivary gland epithelial cell apoptosis in Sjögren's syndrome

Analysis of differentially expressed microRNA of TNF-α-stimulated mesenchymal stem cells and exosomes from their culture supernatant

Primary Sjögren’s syndrome: new perspectives on salivary gland epithelial cells

Contact Info

Product

Resources

About