scholarly journals Resolvin D1 prevents TNF-α-mediated disruption of salivary epithelial formation

2012 ◽  
Vol 302 (9) ◽  
pp. C1331-C1345 ◽  
Author(s):  
Olutayo Odusanwo ◽  
Sreedevi Chinthamani ◽  
Andrew McCall ◽  
Michael E. Duffey ◽  
Olga J. Baker
Keyword(s):  
Cell Migration ◽  
Tight Junction ◽  
Salivary Glands ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Receptor Activation ◽  
Sjogren's Syndrome ◽  
Tnf Α ◽  
Sjögren‘S Syndrome

Sjögren's syndrome is a chronic autoimmune disorder characterized by inflammation of salivary glands resulting in impaired secretory function. Our present studies indicate that chronic exposure of salivary epithelium to TNF-α and/or IFN-γ alters tight junction integrity, leading to secretory dysfunction. Resolvins of the D-series (RvDs) are endogenous lipid mediators derived from DHA that regulate excessive inflammatory responses leading to resolution and tissue homeostasis. In this study, we addressed the hypothesis that activation of the RvD1 receptor ALX/FPR2 in salivary epithelium prevents and/or resolves the TNF-α-mediated disruption of acinar organization and enhances monolayer formation. Our results indicate that 1) the RvD1 receptor ALX/FPR2 is present in fresh, isolated cells from mouse salivary glands and in cell lines of salivary origin; and 2) the agonist RvD1 (100 ng/ml) abolished tight junction and cytoskeletal disruption caused by TNF-α and enhanced cell migration and polarity in salivary epithelium. These effects were blocked by the ALX/FPR2 antagonist butyloxycarbonyl-Phe-Leu-Phe-Leu-Phe. The ALX/FPR2 receptor signals via modulation of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways since, in our study, blocking PI3K activation with LY294002, a potent and selective PI3K inhibitor, prevented RvD1-induced cell migration. Furthermore, Akt gene silencing with the corresponding siRNA almost completely blocked the ability of Par-C10 cells to migrate. Our findings suggest that RvD1 receptor activation promotes resolution of inflammation and tissue repair in salivary epithelium, which may have relevance in the restoration of salivary gland dysfunction associated with Sjögren's syndrome.

scholarly journals Targeted TNF-α Overexpression Drives Salivary Gland Inflammation

2019 ◽  
Vol 98 (6) ◽  
pp. 713-719 ◽  
Author(s):  
A. Limaye ◽  
B.E. Hall ◽  
L. Zhang ◽  
A. Cho ◽  
M. Prochazkova ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Salivary Glands ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Genetic Recombination ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Aquaporin 5 ◽  
Tnf Α ◽  
Sjögren‘S Syndrome

Chronic inflammation of the salivary glands from pathologic conditions such as Sjögren’s syndrome can result in glandular destruction and hyposalivation. To understand which molecular factors may play a role in clinical cases of salivary gland hypofunction, we developed an aquaporin 5 (AQP5) Cre mouse line to produce genetic recombination predominantly within the acinar cells of the glands. We then bred these mice with the TNF-αglo transgenic line to develop a mouse model with salivary gland–specific overexpression of TNF-α; which replicates conditions seen in sialadenitis, an inflammation of the salivary glands resulting from infection or autoimmune disorders such as Sjögren’s syndrome. The resulting AQP5-Cre/TNF-αglo mice display severe inflammation in the salivary glands with acinar cell atrophy, fibrosis, and dilation of the ducts. AQP5 expression was reduced in the salivary glands, while tight junction integrity appeared to be disrupted. The immune dysregulation in the salivary gland of these mice led to hyposalivation and masticatory dysfunction.

Expression of pro-inflammatory TACE-TNF-α-amphiregulin axis in Sjögren’s syndrome salivary glands

2010 ◽  
Vol 134 (4) ◽  
pp. 345-353 ◽  
Author(s):  
Margherita Sisto ◽  
Sabrina Lisi ◽  
Dario Domenico Lofrumento ◽  
Giuseppe Ingravallo ◽  
Vincenzo Mitolo ◽  
...  
Keyword(s):  
Salivary Glands ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Tnf Α ◽  
Sjögren‘S Syndrome

Interleukin-17 Impairs Salivary Tight Junction Integrity in Sjögren’s Syndrome

2016 ◽  
Vol 95 (7) ◽  
pp. 784-792 ◽  
Author(s):  
L.W. Zhang ◽  
X. Cong ◽  
Y. Zhang ◽  
T. Wei ◽  
Y.C. Su ◽  
...  
Keyword(s):  
Tight Junction ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Interleukin 17 ◽  
Sjögren‘S Syndrome

scholarly journals Interferon gamma-inducible protein 16 (IFI16) and anti-IFI16 antibodies in primary Sjögren’s syndrome: findings in serum and minor salivary glands

Reumatismo ◽  
2016 ◽  
Vol 67 (3) ◽  
pp. 85 ◽  
Author(s):  
A. Alunno ◽  
V. Caneparo ◽  
F. Carubbi ◽  
O. Bistoni ◽  
S. Caterbi ◽  
...  
Keyword(s):  
Salivary Glands ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Primary Sjögren’S Syndrome ◽  
Minor Salivary Glands ◽  
Primary Sjogren’S Syndrome ◽  
Primary Sjögren's Syndrome ◽  
Sjögren‘S Syndrome

The interferon (IFN) signature, namely the overexpression of IFN-inducible genes is a crucial aspect in the pathogenesis of primary Sjögren’s syndrome (pSS). The IFN-inducible IFI16 protein, normally expressed in cell nuclei, may be overexpressed, mislocalized in the cytoplasm and secreted in the extracellular milieu in several autoimmune disorders including pSS. This leads to tolerance breaking to this self-protein and development of anti-IFI16 antibodies. The aim of this study was to identify pathogenic and clinical significance of IFI16 and anti-IFI16 autoantibodies in pSS. IFI16 and anti-IFI16 were assessed in the serum of 30 pSS patients and one-hundred healthy donors (HD) by ELISA. IFI16 was also evaluated in 5 minor salivary glands (MSGs) of pSS patients and 5 MSGs of non-pSS patients with sicca symptoms by immunohistochemistry. Normal MSGs do not constitutively express IFI16. Conversely, in pSS-MSGs a marked expression and cytoplasmic mislocalization of IFI16 by epithelial cells was observed with infiltrations in lymphocytes and peri/ intra-lesional endothelium. pSS patients display higher serum levels of both IFI16 and anti-IFI16 autoantibodies compared to HD. Our data suggest that IFI16 protein may be involved in the initiation and perpetuation of glandular inflammation occurring in pSS.

Interdisciplinary approach to the management of a patient with Sjogren’s syndrome: a clinical case

2021 ◽  
Author(s):  
N. Y. Emelyanova ◽  
T. E. Kozyrieva ◽  
O. V. Stepanova ◽  
N. V. Zorenko
Keyword(s):  
Oral Cavity ◽  
Salivary Glands ◽  
Sjögren’S Syndrome ◽  
Clinical Case ◽  
Sjögren's Syndrome ◽  
Interdisciplinary Approach ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Mucous Membranes ◽  
Sjögren‘S Syndrome

Dryness of the mucous membranes (in mouth, nose, genitals in women) and skin are the most common complaints of patients with Sjogren’s disease — a multisystem immune‑mediated disorder that causes anxiety and concern associated with the difficulties of initial diagnosis. The authors present a clinical case of a patient with primary Sjogren’s syndrome, a large number of symptoms of digestive diseases, complaints of dryness of mucous membranes, in particular the oral cavity. The diagnosis was confirmed by allied specialists such as ophthalmologist, gynecologist, rheumatologist, dentist. Detailed dental examination revealed the main dental complaints (constant dry mouth, galitos, changes in taste), clinical condition (dryness of the red border of the lips, swelling of the oral mucosa, changes in the relief of the gums), decreased secretory activity and significant reduction of unstimulated salivation with a moderate level of stimulated salivation. It is noted that a significant decrease in sialometry (0.01 ml per minute) and functional activity of the small salivary glands (up to 18) confirms the presence of true xerostomia. Micro‑crystallization of saliva revealed disorganization of irregularly shaped structures, as well as a significant number of organic inclusions, which indicates a violation of homeostasis in the oral cavity. Given the results of ultrasound examination of the large salivary glands and the absence of enlargement and swelling of the glands during clinical examination, we can assume that the destructive damage to the glands is not so pronounced, evacuation function of the gland is not reduced, but the amount of secretion is significantly reduced. To provide medical aid to patients with Sjogren’s syndrome, the accessibility of the qualified consultation is important and required, with conduction of comprehensive examinations by allied specialists, including a dentist.  

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