Effect of VIP on TLR2 and TLR4 Expression in Lymph Node Immune Cells During TNBS‐Induced Colitis

Arranz, Alicia; Abad, Catalina; Juarranz, Yasmina; Torroba, M.; Rosignoli, Florencia; Leceta, Javier; Gomariz, Rosa P.; Martı́nez, Carmen

doi:10.1196/annals.1317.001

Cited by 30 publications

(22 citation statements)

References 13 publications

(13 reference statements)

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“…Some studies, [254,255,256], have reported that administration of VIP ameliorated the trinitrobenzensulfonic acid (TNBS)-induced experimental colitis, a murine model of human CD associated with down-regulation of Th1-driven autoimmune responses and modifying IL-1, IL-6, TNF-and IFN-expression as well as increasing the antiinflammatory IL-10 and the Th2 cytokine IL-4. The same authors amplify the antiinflammatory mechanism of VIP by reducing TLR-2 and TLR-4 expression on macrophages, T cells, and DCs [257]. Newman et al [258] have found divergent data where, in a comparable animal model of intestinal inflammation, VIP was unable to ameliorate the clinical and histopathological markers of disease and to modify/regulate the Th1/Th2 cytokine profile in TNBS-challenged mice.…”

Section: In Vitro and Experimental Ibd Studiesmentioning

confidence: 94%

Intestinal Immunomodulation. Role of Regulative Peptides and Promising Pharmacological Activities

Motilva

Talero²,

Calvo³

et al. 2008

CPD

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About 50 peptides, and a similar number of peptide receptors, are known to be present in the gut and this amount is likely to rise significantly over the next few years. While there has been a massive research effort to define their functions and their anatomical distribution in the central nervous system (CNS), the understanding of their roles in the gut is far more limited. Classically, the physiological functions include the control of motility, fluids, electrolytes, and digestive enzymes secretion, or vascular and visceral pain function, and more recently, the role-played in cell proliferation and survival, and in immune-inflammatory responses. The term inflammatory bowel disease (IBD) that encompasses Crohn's disease and ulcerative colitis, is clearly an inflammatory disease where several mediators such as cytokines, chemokines, prostanoids, nitric oxide or free radicals, produced by infiltrating cells, play a critical role in intestine tissue alteration. Some peptides, initially known for their neuroregulative properties, have been suggested to act as endogenous immune factors, with predominant antiinflammatory effects. Based on these actions, these molecules are proposed as potential agents for the treatment of IBD and selective peptide analogs are being developed as novel therapeutic strategies for IBD patients. Patients with IBD have an increased risk for developing colorectal cancer (CRC). Up to the present time, no known genetic basis has been identified to explain CRC predisposition in these IBD. Instead, it is assumed that chronic inflammation is what causes cancer. This is supported by the fact that colon cancer risk increases with longer duration of colitis, greater anatomic extent of colitis, the concomitant presence of other inflammatory manifestations, and the fact that certain drugs used to treat inflammation, may prevent the development of CRC. However, though different regulative peptides play a beneficial role in experimental IBD, an increasing number of articles about cancer pathology are starting to implicate different peptides in tumor initiation and progression. The complexities of cancer could be described in terms of a small number of underlying principles and the malignant growth is dependent upon a multi-step process including different basic essential alterations. The activities of many peptides that are overexpressed in cancer cells help them to develop several of the molecular and physiological features that are now considered the basis of malignant growth. These collective findings implicate regulative peptides, receptors, or peptide-levels modulators, as important biological targets for developing intervention strategies against intestinal immunological disorders and cancers.

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Section: In Vitro and Experimental Ibd Studiesmentioning

confidence: 94%

Intestinal Immunomodulation. Role of Regulative Peptides and Promising Pharmacological Activities

Motilva

Talero²,

Calvo³

et al. 2008

CPD

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“…Indeed, in MLN there was a significant decrease in absolute cell numbers on day 3 and a more drastic one on day 5 after the induction of the disease. Regarding the different cell populations present in MLN, the proportion of M⌽ (CD11b+) and DCs (CD11c+) was increased on days 5 and 7, whereas there was a significant reduction of lymphocytes at these time points [9,10] . Interestingly, the percentage of T CD4+ cells on days 5 and 7 and T CD8+ cells on day 5 was reduced, but TNBS triggered a significant increase in B CD19+ cell number on day 5 ( table 1 ).…”

Section: Cellular Traffic From/to Mesenteric Lymph Nodes: Apcs and T mentioning

confidence: 95%

“…1 ). Treatment with 1 nmol of VIP every other day resulted in an inhibition of this overexpression of TLR2 and TLR4, both approaching steady-state levels [9,10] . Moreover, VIP-induced modulation of TLR expression has been corroborated in human monocytic THP1 cells and peripheral blood monocytes [26] as well as in fibroblast-like synoviocytes from patients with rheumatoid arthritis [27,28] .…”

Section: Validation Of the Therapeutic Utility Through Its Tlr Modulamentioning

confidence: 99%

Vasoactive Intestinal Peptide as a Healing Mediator in Crohn’s Disease

Arranz

Abad

Juarranz

et al. 2008

Neuroimmunomodulation

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The vasoactive intestinal peptide/pituitary adenylate cyclase-activating peptide (VIP/PACAP) system is considered as a paradigm for the use of a neuroendocrine-immune mediator in therapy. We review the role of VIP in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis as a murine model of Crohn’s disease. VIP treatment led to the recovery of clinical factors, the amelioration of parameters related to the recruitment and traffic of cell populations, and the balance of inflammatory mediators derived from granulocytes, antigen-presenting cells and T lymphocytes including Th1, Th2 and Th17. Finally, the most recent data validate its therapeutic role through the modulation of TLR2 and 4 receptors.

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“…Treatment with VIP decreased the levels of a wide array of chemokines and proinflammatory cytokines [14]. In addition, VIP downregulated the expression of toll-like receptors (TLR)-2 and 4 in the colon and mesenteric lymph nodes of TNBS-treated animals [15,16]. These latter receptors have been depicted as innate immune sensors of bacterial and other pathogen components and have been implicated in inflammatory responses.…”

Section: Introductionmentioning

confidence: 99%

Vasoactive Intestinal Peptide-Deficient Mice Exhibit Reduced Pathology in Trinitrobenzene Sulfonic Acid-Induced Colitis

Cheung-Lau¹,

Coûté-Monvoisin²,

Waschek³

2014

Neuroimmunomodulation

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Objectives: Vasoactive intestinal peptide (VIP) is an immunomodulatory neuropeptide with therapeutic properties in multiple murine models of inflammatory disease including the trinitrobenzene-sulfonic acid (TNBS)-colitis model of Crohn's disease. Understanding the spectrum of biological actions of endogenously produced VIP may help us dissect the complex and multifactorial pathogenesis of such inflammatory diseases. Our goal was to determine the contribution of endogenously produced VIP to TNBS-colitis by using VIP knockout (KO) mice. Methods: TNBS was intracolonically administered to wild-type (WT) and VIP KO mice, and weight loss and colitis were assessed over time. Colon histopathological changes and myeloperoxidase activities were analyzed and the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in colon and serum quantified. The proliferative response in vitro of splenocytes from TNBS WT and VIP KO administered mice to anti-CD3 and anti-CD28 was determined. Results: VIP KO mice did not exhibit the predicted exacerbated response to TNBS. Instead, they developed a milder clinical profile than WT mice, with lower TNF-α and IL-6 levels. Such potential defects seem selective, because other parameters such as the histopathological scores and the cytokine levels in the colon did not differ between the two strains of mice. Moreover, splenocytes from TNBS-treated VIP KO mice exhibited an enhanced proliferative response to anti-CD3/CD28 stimulation in vitro. Conclusion: Chronic loss of VIP in mice leads to a disruption of certain but not all immunological compartments, corroborating recent findings that VIP KO mice exhibit reduced mortality in the lipopolysaccharide-induced endotoxemia model and attenuated clinical development of experimental autoimmune encephalomyelitis while developing robust T-cell responses.

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Effect of VIP on TLR2 and TLR4 Expression in Lymph Node Immune Cells During TNBS‐Induced Colitis

Cited by 30 publications

References 13 publications

Intestinal Immunomodulation. Role of Regulative Peptides and Promising Pharmacological Activities

Intestinal Immunomodulation. Role of Regulative Peptides and Promising Pharmacological Activities

Vasoactive Intestinal Peptide as a Healing Mediator in Crohn’s Disease

Vasoactive Intestinal Peptide-Deficient Mice Exhibit Reduced Pathology in Trinitrobenzene Sulfonic Acid-Induced Colitis

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