The anti-inflammatory effect of neuropeptide Y (NPY) in rats is dependent on dipeptidyl peptidase 4 (DP4) activity and age

Dimitrijević, Mirjana; Stanojević, Stanislava; Mitić, Katarina; Kuštrimović, Nataša; Vujić, Vesna; Miletić, Tatjana; Kovačević-Jovanović, Vesna

doi:10.1016/j.peptides.2008.08.017

Cited by 45 publications

(25 citation statements)

References 52 publications

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“…In agreement with this, the expression of DPP4, which cleaves NPY to a form that preferentially binds Y2R over Y1R, by monocytes also contributes to the anti-inflammatory effects of NPY (49). The ability of Y2R-specific NPY to inhibit retrovirus-induced neurological disease correlates with Y2R expression on monocytes.…”

Section: Discussionsupporting

confidence: 52%

Neuropeptide Y Negatively Influences Monocyte Recruitment to the Central Nervous System during Retrovirus Infection

Woods

Carmody

et al. 2016

J Virol

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Monocyte infiltration into the CNS is a hallmark of several viral infections of the central nervous system (CNS), including retrovirus infection.Understanding the factors that mediate monocyte migration in the CNS is essential for the development of therapeutics that can alter the disease process. In the current study, we found that neuropeptide Y (NPY) suppressed monocyte recruitment to the CNS in a mouse model of polytropic retrovirus infection. NPY ؊/؊ mice had increased incidence and kinetics of retrovirus-induced neurological disease, which correlated with a significant increase in monocytes in the CNS compared to wildtype mice. Both Ly6C hi inflammatory and Ly6C lo alternatively activated monocytes were increased in the CNS of NPY ؊/؊ mice following virus infection, suggesting that NPY suppresses the infiltration of both cell types. Ex vivo analysis of myeloid cells from brain tissue demonstrated that infiltrating monocytes expressed high levels of the NPY receptor Y2R. Correlating with the expression of Y2R on monocytes, treatment of NPY ؊/؊ mice with a truncated, Y2R-specific NPY peptide suppressed the incidence of retrovirus-induced neurological disease. These data demonstrate a clear role for NPY as a negative regulator of monocyte recruitment into the CNS and provide a new mechanism for suppression of retrovirus-induced neurological disease. IMPORTANCEMonocyte recruitment to the brain is associated with multiple neurological diseases. However, the factors that influence the recruitment of these cells to the brain are still not well understood. In the current study, we found that neuropeptide Y, a protein produced by neurons, affected monocyte recruitment to the brain during retrovirus infection. We show that mice deficient in NPY have increased influx of monocytes into the brain and that this increase in monocytes correlates with neurological-disease development. These studies provide a mechanism by which the nervous system, through the production of NPY, can suppress monocyte trafficking to the brain and reduce retrovirus-induced neurological disease. The recruitment of monocytes into the central nervous system (CNS) is associated with a number of neurological diseases. Monocyte recruitment to the CNS has been reported for traumatic brain injury (TBI), misfolded-protein diseases, and multiple sclerosis (MS), as well as many different viral infections, including West Nile virus (WNV), herpes simplex virus (HSV), and retroviruses, such as HIV (1-4). Monocyte trafficking is particularly important for retrovirus-induced neurological diseases, as monocytes are susceptible to retrovirus infection (5, 6).Monocytes recruited to the CNS may contribute to pathogenesis in these neurological diseases. Decreased cognitive performance correlated with increased monocyte infiltration in HIVassociated neurocognitive disorders (HAND) (1). Additionally, infiltration of monocytes was found to be important for seizure development in a mouse model of Theiler's murine encephalitis (7). Recent studies in a mouse mo...

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Section: Discussionsupporting

confidence: 52%

Neuropeptide Y Negatively Influences Monocyte Recruitment to the Central Nervous System during Retrovirus Infection

Woods

Carmody

et al. 2016

J Virol

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“…It has been reported that this SNP is due to the loss of a transcriptional factor (Sp1) binding consensus by substitution G to A [23]. However, another study [24] reported that the effect on NPY expression might be caused by the interaction of the G/A allele with another regulatory genomic DNA regions different from Sp1.…”

Section: Discussionmentioning

confidence: 99%

Polymorphism rs16147 of the Neuropeptide Y Gene Modifies the Response of Cardiovascular Risk Biomarkers and Adipokines to Two Hypocaloric Diets

Luis

Izaola²,

Primo³

et al. 2017

Lifestyle Genomics

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Aims: Our aim was to evaluate the relationship of weight loss and changes in adipokine levels after two hypocaloric diets in obese subjects with polymorphism rs16147 of the neuropeptide Y gene. Subjects and Methods: A population of 283 obese patients was analyzed. At the basal visit, patients were randomly allocated to one of two diets for a period of 3 months (diet I, low in carbohydrates; diet II, low in fat). Results: With diet I and in both genotype groups (major versus minor allele), body mass index (BMI), weight, fat mass, waist circumference, and leptin decreased. With diet II and in all genotypes, BMI, weight, fat mass, waist circumference, and leptin decreased. With both diets and in subjects with the minor allele, insulin levels (diet I: major allele -1.7 ± 7.8 IU/L versus minor allele -4.2 ± 6.1 IU/L, p = 0.01; diet II: major allele -2.3 ± 6.1 IU/L versus minor allele -4.0 ± 5.2 IU/L, p = 0.02) and insulin resistance (diet I: major allele -0.2 ± 3.1 units versus minor allele -1.7 ± 3.0 units, p = 0.03; diet II: major allele -0.9 ± 2.0 units versus minor allele -1.7 ± 1.3 units, p = 0.01) decreased. Conclusion: The rs16147 genotype affected the reduction in insulin resistance and insulin levels in response to two different hypocaloric diets in obese subjects, with a lack of response in subjects with the major allele.

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“…The use of NPY-related peptides and Y receptor-specific antagonists revealed that the anti-inflammatory effect of NPY is mediated via Y1 and Y5 receptors [44]. Ingested (oral) NPY inhibited ongoing disease and decreased inflammation in actively fed mice.…”

Section: Discussionmentioning

confidence: 99%

Neuropeptide Analysis of Oral Mucosa in Diabetic Rats

Kispélyi¹,

Lohinai²,

Altdorfer³

et al. 2014

Neuroimmunomodulation

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Objective: Increasing evidence indicates that different neuropeptide-containing nerve elements are involved in the immune system and influence the inflammation of the gastrointestinal tract. The aim of this study was to investigate the morphological localization and distribution of the different immunoreactive (IR) nerve fibers and immunocompetent cells in the oral mucosa (e.g. tongue, gingiva) and compare the results with data received from streptozotocin (STZ)-induced diabetic rats. Materials and Methods: The different nerve elements and immunocytes were detected by ABC immunohistochemistry. Results: The IR nerve fibers were found in the tunica propria of oral mucosa with different densities. These IR nerve fibers were mainly located beneath the epithelial lining, around the blood vessels and glands, and some of them were also located in the taste buds. After 2 weeks of STZ treatment the total number of IR nerve fibers, especially the SP and neuropeptide Y (NPY) IR ones, was significantly increased (p < 0.05), as was also the number of immunocytes (lymphocytes, plasma cells, mast cells). Some of these cells also showed immunoreactivity for substance P (SP) and NPY. In several cases the SP IR nerve fibers were found in close proximity to the immunocytes. Electron microscopic investigation also revealed the close association between the IR nerve fibers and immunocompetent cells where the gap was 1 µm or even less. Conclusions: The close anatomical associations suggest communication between nerve fibers and immune cells which can be crucial for maintaining mucosal homeostasis and for ensuring an appropriate response to injury.

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The anti-inflammatory effect of neuropeptide Y (NPY) in rats is dependent on dipeptidyl peptidase 4 (DP4) activity and age

Cited by 45 publications

References 52 publications

Neuropeptide Y Negatively Influences Monocyte Recruitment to the Central Nervous System during Retrovirus Infection

Neuropeptide Y Negatively Influences Monocyte Recruitment to the Central Nervous System during Retrovirus Infection

Polymorphism <b><i>rs16147</i></b> of the <b><i>Neuropeptide Y</i></b> Gene Modifies the Response of Cardiovascular Risk Biomarkers and Adipokines to Two Hypocaloric Diets

Neuropeptide Analysis of Oral Mucosa in Diabetic Rats

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