Vasoactive intestinal peptide/vasoactive intestinal peptide receptor relative expression in salivary glands as one endogenous modulator of acinar cell apoptosis in a murine model of Sjögren's syndrome

Hauk, Vanesa; Calafat, Mario Jose; Larocca, Luciana; Fraccaroli, Laura Virginia; Grasso, Esteban; Ramhorst, Rosanna; Leirós, Claudia Pérez

doi:10.1111/j.1365-2249.2011.04478.x

Cited by 14 publications

(15 citation statements)

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“…Consistently, VIP promoted an alternative activation profile in NOD mice macrophages and favoured a suppressant apoptotic cell clearance by NOD macrophages [26,27]. However, which biological circuits will be mediated preferentially by VIP in vivo is not easily predictable, as was shown clearly by Abad and coworkers in VIP knock-out mice that are resistant to experimental autoimmune encephalitis and LPS-induced endotoxaemia [44,45].…”

Section: Discussionmentioning

confidence: 70%

“…Consistently, evidence on an impaired or delayed clearance of apoptotic cells by macrophages was reported in systemic lupus erythematosus (SLE) patients, although its direct aetiopathogenic role is still unclear [22][23][24]. Regarding SS, a deficient phagocytosis of apoptotic cells was described in the non-obese diabetic (NOD) mouse model of the disease [25][26][27]. In particular, macrophages isolated from NOD mice at the SS-like stage expressed a predominant M1 inflammatory activation profile and presented a defective engulfment of apoptotic acinar cells [26].…”

Section: Introductionmentioning

confidence: 79%

“…Regarding SS, a deficient phagocytosis of apoptotic cells was described in the non-obese diabetic (NOD) mouse model of the disease [25][26][27]. In particular, macrophages isolated from NOD mice at the SS-like stage expressed a predominant M1 inflammatory activation profile and presented a defective engulfment of apoptotic acinar cells [26].…”

Section: Introductionmentioning

confidence: 99%

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Monocytes from Sjögren's syndrome patients display increased vasoactive intestinal peptide receptor 2 expression and impaired apoptotic cell phagocytosis

Hauk

Fraccaroli

Grasso

et al. 2014

Clinical and Experimental Immunology

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SummarySjögren's syndrome (SS) is a chronic autoimmune disease characterized by salivary and lacrimal gland dysfunction. Clinical observations and results from animal models of SS support the role of aberrant epithelial cell apoptosis and immune homeostasis loss in the glands as triggering factors for the autoimmune response. Vasoactive intestinal peptide (VIP) promotes potent anti-inflammatory effects in several inflammatory and autoimmune disease models, including the non-obese diabetic (NOD) mouse model of SS. With the knowledge that VIP modulates monocyte function through vasoactive intestinal peptide receptors (VPAC) and that immune homeostasis maintenance depends strongly upon a rapid and immunosuppressant apoptotic cell clearance by monocytes/macrophages, in this study we explored VPAC expression on monocytes from primary SS (pSS) patients and the ability of VIP to modulate apoptotic cell phagocytic function and cytokine profile. Monocytes isolated from individual pSS patients showed an increased expression of VPAC2 subtype of VIP receptors, absent in monocytes from control subjects, with no changes in VPAC1 expression. VPAC2 receptor expression could be induced further with lipopolysaccharide (LPS) in pSS monocytes and VIP inhibited the effect. Moreover, monocytes from pSS patients showed an impaired phagocytosis of apoptotic epithelial cells, as evidenced by reduced engulfment ability and the failure to promote an immunosuppressant cytokine profile. However, VIP neither modulated monocyte/macrophage phagocytic function nor did it reverse their inflammatory profile. We conclude that monocytes from pSS patients express high levels of VPAC2 and display a deficient clearance of apoptotic cells that is not modulated by VIP.

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Section: Discussionmentioning

confidence: 70%

Section: Introductionmentioning

confidence: 79%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Monocytes from Sjögren's syndrome patients display increased vasoactive intestinal peptide receptor 2 expression and impaired apoptotic cell phagocytosis

Hauk

Fraccaroli

Grasso

et al. 2014

Clinical and Experimental Immunology

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“…Thus, NOD mice are considered an ideal animal model for SS research. It has been shown that SS symptoms gradually worsen over time and that VIP expression in submandibular glands is reduced with disease progression, which suggests that significant decreases in VIP may be a key indicator of SS disease onset [16]. However, the effects of VIP treatment on SS disease have not been fully elucidated.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have shown that significantly decreased VIP is a factor in SS onset. In the submandibular glands of SS patients and mice, gradual decreases in VIP are seen as disease severity increases, which are related to SS pathogenesis (Th17/Treg immune imbalance) [16, 17]. In addition, AQP5 mRNA and protein expression in rat sweat glands parallels VIP immunoreactivity [18].…”

Section: Introductionmentioning

confidence: 99%

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

Zhu

et al. 2017

Neuroimmunomodulation

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Objective: Sjögren syndrome (SS) is an autoimmune disease involving exocrine glands. Currently, drugs that can improve both abnormal immunity and exocrine gland function are needed. The study aimed to investigate the effect and mechanism of vasoactive intestinal peptide (VIP) on the immune response and exocrine gland function in SS. Methods: We investigated the effects of VIP on the immune response and secretory function of submandibular glands using NOD mice, and analyzed the expression of IL-17A and AQP5 (aquaporin 5). The submandibular gland cells from healthy 8-day-old Sprague-Dawley rats were used to observe the influence of VIP on AQP5 expression. Results: Our study shows that treatment with VIP in an SS mouse model could not only reduce the immune injury to exocrine glands but also improve the secretory function of these glands. Furthermore, VIP was shown to improve the abnormal immune status by downregulating IL-17A expression in the exocrine glands. It also enhanced the secretory function of exocrine glands by upregulating AQP5 expression. Conclusions: Using a model of SS, we found that VIP could not only modulate the immune response but also affect exocrine gland function, and that these therapeutic effects were associated with IL-17A and AQP5 regulation.

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Modes and Mechanisms of Salivary Gland Epithelial Cell Death in Sjogren's Syndrome

et al. 2023

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Sjogren's syndrome is an autoimmune disease in middle and old‐aged women with a dry mucosal surface, which is caused by the dysfunction of secretory glands, such as the oral cavity, eyeballs, and pharynx. Pathologically, Sjogren's syndrome are characterized by lymphocyte infiltration into the exocrine glands and epithelial cell destruction caused by autoantibodies Ro/SSA and La/SSB. At present, the exact pathogenesis of Sjogren's syndrome is unclear. Evidence suggests epithelial cell death and the subsequent dysfunction of salivary glands as the main causes of xerostomia. This review summarizes the modes of salivary gland epithelial cell death and their role in Sjogren's syndrome progression. The molecular mechanisms involved in salivary gland epithelial cell death during Sjogren's syndrome as potential leads to treating the disease are also discussed.

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Vasoactive intestinal peptide/vasoactive intestinal peptide receptor relative expression in salivary glands as one endogenous modulator of acinar cell apoptosis in a murine model of Sjögren's syndrome

Cited by 14 publications

References 40 publications

Monocytes from Sjögren's syndrome patients display increased vasoactive intestinal peptide receptor 2 expression and impaired apoptotic cell phagocytosis

Monocytes from Sjögren's syndrome patients display increased vasoactive intestinal peptide receptor 2 expression and impaired apoptotic cell phagocytosis

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

Modes and Mechanisms of Salivary Gland Epithelial Cell Death in Sjogren's Syndrome

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