The neuropeptide receptor subunit RAMP1 constrains the innate immune response during acute pancreatitis in mice

Jochheim, Leonie; Odysseos, Georgios; Hidalgo-Sastre, Ana; Zhong, Suyang; Staufer, Lina M.; Kroiss, Markus; Kabacaoğlu, Derya; Lange, Sebastian; Engleitner, Thomas; Hüser, Norbert; Steiger, Katja; Schmid, Roland M.; Holzmann, Bernhard; Figura, Guido von

doi:10.1016/j.pan.2019.05.455

Cited by 9 publications

(10 citation statements)

References 46 publications

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“…33 Although the neutrophils and macrophages are responsible for the innate immune system, the T cells assume an essential role in the adaptive immune response. 34 As evident in recent literature, the T cells have vital functions in the immune response. The T helper cells, a subset of CD4+ T cells, induce a special immune response.…”

Section: Discussionmentioning

confidence: 97%

Emodin Alleviates Intestinal Barrier Dysfunction by Inhibiting Apoptosis and Regulating the Immune Response in Severe Acute Pancreatitis

et al. 2021

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Objective:The intestinal barrier injury caused by severe acute pancreatitis (SAP) can induce enterogenous infection, further aggravating the inflammatory reactions and immune responses. This study aimed to test the hypothesis that emodin protects the intestinal function and is involved in the immune response in SAP. Methods:The network pharmacology was established using the Swiss target prediction and pathway enrichment analysis. The SAP mice model was induced by cerulein (50 μg/kg) and lipopolysaccharide (10 mg/kg) hyperstimulation. The pharmacological effect of emodin in treating SAP was evaluated at mRNA and protein levels by various methods. Results:The network analysis provided the connectivity between the targets of emodin and the intestinal barrier-associated proteins and predicted the BAX/Bcl-2/caspase 3 signaling pathway. Emodin alleviated the pathological damages to the pancreas and intestine and reduced the high concentrations of serum amylase and cytokines in vivo. Emodin increased the expression of intestinal barrier-related proteins and reversed the changes in the apoptosis-related proteins in the intestine. Simultaneously, emodin regulated the ratio of T helper type 1 (T H 1), T H 2, T H 17, γδ T cells, and interferon γ/interleukin 17 producing γδ T cells.Conclusions: These findings partly verified the mechanism underlying the regulation of the intestinal barrier and immune response by emodin.

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Section: Discussionmentioning

confidence: 97%

Emodin Alleviates Intestinal Barrier Dysfunction by Inhibiting Apoptosis and Regulating the Immune Response in Severe Acute Pancreatitis

et al. 2021

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“…Glucose tolerance testing was performed in a subset of adult mice and did not demonstrate any changes in glucose handling in the OGT Panc+/− mice (Figure 1F). Additionally, pancreas weight was obtained with consideration of saline vs. cerulein treatment, as it was expected that the induction of acute pancreatitis would increase pancreas weight, which was confirmed for both genotypes (controls (Ctrl), p ≤ 0.001; OGT Panc+/− , p ≤ 0.001) (Figure 1G) [32]. Importantly, there was no difference in pancreas weight within the treatment groups.…”

Section: Body Weight Pancreas Weight and Non-fasted Blood Glucose Was...mentioning

confidence: 57%

Reduction in O-GlcNAcylation Mitigates the Severity of Inflammatory Response in Cerulein-Induced Acute Pancreatitis in a Mouse Model

Moore

Avula

Wong

et al. 2022

Biology

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Acute pancreatitis (AP) involves premature trypsinogen activation, which mediates a cascade of pro-inflammatory signaling that causes early stages of pancreatic injury. Activation of the transcription factor κB (NF-κB) and secretion of pro-inflammatory mediators are major events in AP. O-GlcNAc transferase (OGT), a stress-sensitive enzyme, was recently implicated to regulate NF-κB activation and inflammation in AP in vitro. This study aims to determine whether a pancreas-specific transgenic reduction in OGT in a mouse model affects the severity of AP in vivo. Mice with reduced pancreatic OGT (OGTPanc+/−) at 8 weeks of age were randomized to cerulein, which induces pancreatitis, or saline injections. AP was confirmed by elevated amylase levels and on histological analysis. The histological scoring demonstrated that OGTPanc+/− mice had decreased severity of AP. Additionally, serum lipase, LDH, and TNF-α in OGTPanc+/− did not significantly increase in response to cerulein treatment as compared to controls, suggesting attenuated AP induction in this model. Our study reveals the effect of reducing pancreatic OGT levels on the severity of pancreatitis, warranting further investigation on the role of OGT in the pathology of AP.

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“…The commonly used methods include commercial detection kits [61], enzyme-linked immunosorbent assay (ELISA) [27,49], and immunofluorescence [54]. In addition, for mice and rats AP models, MPO-positive cells, or Ly6G-positive cells in pancreatic tissues, which are commonly used markers of neutrophils, can also be detected by immunohistochemistry [21,28,66].…”

Section: Neutrophils Infiltration In the Pathogenesis Of Ap And Therapymentioning

confidence: 99%

“…Inhibition of Ras signaling by farnesylthiosalicylic acid (FTS) can also attenuate SAP by reducing neutrophil infiltration [63]. Loss of tissue nonspecific alkaline phosphatase (TNAP) [56] or receptor-activity-modifying-protein-1 (RAMP1) [67] expression markedly increase neutrophil infiltration and tissue damage in AP, thus maintaining their expression may be a therapeutic strategy. Several widely studied or novel medications, including 4-phenyl butyric acid (4-PBA) [62], lactose [64], pentoxifylline [72], zileuton [27], desoxo-narchinol-A [59], Evasin-3 [76], biomimetic carbon monoxide delivery [48] and Emodin [53], can abrogate pancreatic neutrophil infiltration and associated inflammation in AP.…”

Section: Neutrophils Infiltration In the Pathogenesis Of Ap And Therapymentioning

confidence: 99%

“…Like neutrophils, macrophages are also the main innate immune cells involved in the pathogenesis of AP, infiltrating the inflamed pancreas in the early phase of AP and promoting the development of AP [19-21, 48, 91, 106-128] (Figure 2). Detection of F4/80 positive cells or CD68 positive cells in the pancreas by immunofluorescence or immunohistochemistry is the main method to detect pancreatic infiltrating macrophages in mice [67,106,129].…”

Section: Macrophages Infiltration In the Pathogenesis Of Ap And Therapymentioning

confidence: 99%

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The Role of Pancreatic Infiltrating Innate Immune Cells in Acute Pancreatitis

Pan¹,

Li²,

Yu³

2021

Int. J. Med. Sci.

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Acute pancreatitis (AP) is a leading cause of gastrointestinal-related hospital admissions with significant morbidity and mortality. Although the underlying pathophysiology of AP is rather complex, which greatly limits the treatment options, more and more studies have revealed that infiltrating immune cells play a critical role in the pathogenesis of AP and determine disease severity. Thus, immunomodulatory therapy targeting immune cells and related inflammatory mediators is expected to be a novel treatment modality for AP which may improve the prognosis of patients. Cells of the innate immune system, including macrophages, neutrophils, dendritic cells, and mast cells, represent the majority of infiltrating cells during AP. In this review, an overview of different populations of innate immune cells and their role during AP will be discussed, with a special focus on neutrophils and macrophages.

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The neuropeptide receptor subunit RAMP1 constrains the innate immune response during acute pancreatitis in mice

Cited by 9 publications

References 46 publications

Emodin Alleviates Intestinal Barrier Dysfunction by Inhibiting Apoptosis and Regulating the Immune Response in Severe Acute Pancreatitis

Emodin Alleviates Intestinal Barrier Dysfunction by Inhibiting Apoptosis and Regulating the Immune Response in Severe Acute Pancreatitis

Reduction in O-GlcNAcylation Mitigates the Severity of Inflammatory Response in Cerulein-Induced Acute Pancreatitis in a Mouse Model

The Role of Pancreatic Infiltrating Innate Immune Cells in Acute Pancreatitis

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