Vasoactive Intestinal Peptide Protects Salivary Glands against Structural Injury and Secretory Dysfunction via IL-17A and AQP5 Regulation in a Model of Sjögren Syndrome

Li, Chengyin; Zhu, Fenglin; Wu, Bin; Wang, Yue

doi:10.1159/000486859

Cited by 11 publications

(12 citation statements)

References 27 publications

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“…IL-17 has been recently reported to play a role in epithelial–mesenchymal transition in SGECs from SS patients [ 70 ]. Vasoactive intestinal peptide (VIP) administration to NOD mice protects SG against injury and secretory dysfunction by downregulating Il-17 expression and upregulating Aqp5 expression [ 71 ]. Blocking IL-7-induced levels reduced SG inflammation and hypofunction [ 72 ], and upregulated AQP5 expression [ 73 ].…”

Section: Involvement Of Aqps In Sg Pathologiesmentioning

confidence: 99%

Insight into Salivary Gland Aquaporins

D’Agostino

Elkashty

Chivasso

et al. 2020

Cells

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The main role of salivary glands (SG) is the production and secretion of saliva, in which aquaporins (AQPs) play a key role by ensuring water flow. The AQPs are transmembrane channel proteins permeable to water to allow water transport across cell membranes according to osmotic gradient. This review gives an insight into SG AQPs. Indeed, it gives a summary of the expression and localization of AQPs in adult human, rat and mouse SG, as well as of their physiological role in SG function. Furthermore, the review provides a comprehensive view of the involvement of AQPs in pathological conditions affecting SG, including Sjögren’s syndrome, diabetes, agedness, head and neck cancer radiotherapy and SG cancer. These conditions are characterized by salivary hypofunction resulting in xerostomia. A specific focus is given on current and future therapeutic strategies aiming at AQPs to treat xerostomia. A deeper understanding of the AQPs involvement in molecular mechanisms of saliva secretion and diseases offered new avenues for therapeutic approaches, including drugs, gene therapy and tissue engineering. As such, AQP5 represents a potential therapeutic target in different strategies for the treatment of xerostomia.

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Section: Involvement Of Aqps In Sg Pathologiesmentioning

confidence: 99%

Insight into Salivary Gland Aquaporins

D’Agostino

Elkashty

Chivasso

et al. 2020

Cells

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“…Li et al showed that VIP treatment was able to reduce immune lesions in the exocrine glands and improve the secretory function of these glands by negatively regulating the expression of IL-17A in the exocrine glands. It also improved the secretory function of the exocrine glands by increasing the expression of AQP5, a protein that participates in the transport of water through the glandular epithelium [301].…”

Section: Other Autoimmune Disordersmentioning

confidence: 99%

A Clinical Approach for the Use of VIP Axis in Inflammatory and Autoimmune Diseases

Martı́nez

Juarranz

Gutiérrez‐Cañas

et al. 2019

IJMS

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The neuroendocrine and immune systems are coordinated to maintain the homeostasis of the organism, generating bidirectional communication through shared mediators and receptors. Vasoactive intestinal peptide (VIP) is the paradigm of an endogenous neuropeptide produced by neurons and endocrine and immune cells, involved in the control of both innate and adaptive immune responses. Exogenous administration of VIP exerts therapeutic effects in models of autoimmune/inflammatory diseases mediated by G-protein-coupled receptors (VPAC1 and VPAC2). Currently, there are no curative therapies for inflammatory and autoimmune diseases, and patients present complex diagnostic, therapeutic, and prognostic problems in daily clinical practice due to their heterogeneous nature. This review focuses on the biology of VIP and VIP receptor signaling, as well as its protective effects as an immunomodulatory factor. Recent progress in improving the stability, selectivity, and effectiveness of VIP/receptors analogues and new routes of administration are highlighted, as well as important advances in their use as biomarkers, contributing to their potential application in precision medicine. On the 50th anniversary of VIP’s discovery, this review presents a spectrum of potential clinical benefits applied to inflammatory and autoimmune diseases.

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“…Vasoactive intestinal peptide (VIP) is a 28-amino acid peptide that is extensively distributed in tissues, which exerts pleiotropic functions in multiple systems, such as the gastrointestinal [7], cardiovascular [8], nervous [9], and immune [10, 11] systems. Many studies have shown that VIP can be used as an immunomodulatory and anti-inflammatory factor that participates in regulating immune balance [10, 12]. It has been reported that VIP can effectively increase the number of Treg subpopulations while decreasing the number of Th17 subpopulations to improve inflammation in asthmatic mice by regulating Th17/Treg balance and VIP can also maintain the immune balance between Th17/Treg cells in the prevention and treatment of experimental autoimmune encephalomyelitis (EAE).…”

Section: Introductionmentioning

confidence: 99%

Vasoactive intestinal peptide ameliorates renal injury in a pristane-induced lupus mouse model by modulating Th17/Treg balance

Senouthai

Wang

et al. 2019

BMC Nephrol

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Background Lupus nephritis (LN) is an inflammation of the kidneys and is a major cause of mortality in systemic lupus erythaematosus (SLE) patients. In addition, Th17/Treg balance is one of the most important factors that can promote the development of LN. It has been reported that vasoactive intestinal peptide (VIP) is associated with the downregulation of both inflammatory and autoimmune diseases through regulating T lymphocyte balance. Therefore, the aim of this study was to determine the role of VIP in modulating Th17/Treg balance in LN. Methods LN was induced in BALB/c female mice by injection pristane. After 3 months, mice were randomly divided into four groups: control, VIP + control, LN and VIP + LN. Autoantibody levels were tested by ELISA. The distribution of Th17/Treg cells in vivo and in vitro was detected by FC. Renal tissues were examined by PASM and DIF for pathology and Foxp3 + CD3 + . The mRNA and protein expression levels of pro- and anti-inflammatory cytokines were detected by qRT-PCR and western blotting. Results VIP can improve renal injury by regulating Th17/Treg imbalance in LN mice. Proteinuria, renal function defects and autoantibodies were significantly decreased, and Th17/Treg cell balance was restored in VIP compared with LN mice. In addition, VIP improved renal lesions by promoting the expression of Foxp3 + CD3 + in renal tissue. Furthermore, VIP downregulated the mRNA and protein expression of IL-17, IL-6 and upregulated Foxp3, IL-10 expression. Conclusions VIP reduced LN proteinuria and renal function defects and restored the Th17/Treg cell balance. Furthermore, VIP also downregulated autoantibody and inflammatory cytokine expression and upregulated Foxp3 and IL-10 expression.

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Vasoactive Intestinal Peptide Protects Salivary Glands against Structural Injury and Secretory Dysfunction via IL-17A and AQP5 Regulation in a Model of Sjögren Syndrome

Cited by 11 publications

References 27 publications

Insight into Salivary Gland Aquaporins

Insight into Salivary Gland Aquaporins

A Clinical Approach for the Use of VIP Axis in Inflammatory and Autoimmune Diseases

Vasoactive intestinal peptide ameliorates renal injury in a pristane-induced lupus mouse model by modulating Th17/Treg balance

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