NEUROPEPTIDES MODULATE A MURINE MONOCYTE/MACROPHAGE CELL LINE CAPACITY FOR PHAGOCYTOSIS AND KILLING OF<i>LEISHMANIA MAJOR</i>PARASITES

Ahmed, Aqeel; Wahbi, A; Nordlin, K

doi:10.1081/iph-100107339

Cited by 42 publications

(22 citation statements)

References 43 publications

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“…There is a growing list of neuropeptides like MCH that modulate monocyte/macrophage functions (15,17). For instance, substance P can elicit a variety of responses in monocytes, including differentiation (18), phagocytosis (15), production of proinflammatory cytokines (19), and chemotaxis (20).…”

Section: Discussionmentioning

confidence: 99%

Increased Susceptibility of Melanin-Concentrating Hormone-Deficient Mice to Infection with Salmonella enterica Serovar Typhimurium

et al. 2013

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bMelanin-concentrating hormone (MCH) was initially identified in mammals as a hypothalamic neuropeptide regulating appetite and energy balance. However, the wide distribution of MCH receptors in peripheral tissues suggests additional functions for MCH which remain largely unknown. We have previously reported that mice lacking MCH develop attenuated intestinal inflammation when exposed to Clostridium difficile toxin A. To further characterize the role of MCH in host defense mechanisms against intestinal pathogens, Salmonella enterocolitis (using Salmonella enterica serovar Typhimurium) was induced in MCHdeficient mice and their wild-type littermates. In the absence of MCH, infected mice had increased mortality associated with higher bacterial loads in blood, liver, and spleen. Moreover, the knockout mice developed more-severe intestinal inflammation, based on epithelial damage, immune cell infiltrates, and local and systemic cytokine levels. Paradoxically, these enhanced inflammatory responses in the MCH knockout mice were associated with disproportionally lower levels of macrophages infiltrating the intestine. Hence, we investigated potential direct effects of MCH on monocyte/macrophage functions critical for defense against intestinal pathogens. Using RAW 264.7 mouse monocytic cells, which express endogenous MCH receptor, we found that treatment with MCH enhanced the phagocytic capacity of these cells. Taken together, these findings reveal a previously unappreciated role for MCH in host-bacterial interactions. Melanin-concentrating hormone (MCH) was initially described in 1983 by Kawauchi to be secreted from the salmon pituitary gland as a stress response to a predator (1). As its name indicates, MCH lightens fish skin color by segregating the pigment-carrying granules in melanocytes. It is highly conserved between species, as human and salmon MCH sequences are almost identical. MCH in mammals has been identified as one of the orexigenic neuropeptides in the hypothalamus, by demonstrating that intracerebroventricular injection of MCH stimulates feeding in rats (2). Subsequent studies revealed that MCH-deficient mice are leaner and resist diet-induced obesity (3-5). Despite the wellestablished role of MCH in energy balance, the distribution of MCH receptor 1 (MCHR1) not only in brain but also in peripheral tissues, including the gastrointestinal tract, indicates additional functions for MCH, which remain largely unexplored.Our group has recently reported that mice deficient for MCH develop attenuated 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis (6), as well as attenuated Clostridium difficile toxin A-mediated enteritis. Moreover, in vitro studies revealed direct proinflammatory effects of MCH on colonic epithelial cells, resulting in upregulation of cytokine expression (6, 7). In mice, MCHR1 transcripts have been detected in spleen, thymus, lymph nodes, bone marrow, and blood, and fluorescence-activated cell sorter (FACS) analysis suggested that human CD3 ϩ cells (T cells), CD19ϩ cells...

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Section: Discussionmentioning

confidence: 99%

Increased Susceptibility of Melanin-Concentrating Hormone-Deficient Mice to Infection with Salmonella enterica Serovar Typhimurium

et al. 2013

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“…However, enhancement of chemotaxis by the SRIF analogue octreotide has been described as well (Ahmed et al, 2001;Ahmed et al, 1998;Wiedermann et al, 1993).…”

Section: Effects Of Srif On the Functions Of Monocytes And Macrophagesmentioning

confidence: 99%

The role of cortistatin in the human immune system

Hagen

Dalm

Staal

et al. 2008

Molecular and Cellular Endocrinology

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Please cite this article as: van Hagen, P.M., Dalm, V.A., Staal, F., Hofland, L.J., The Role of Cortistatin in the Human Immune System, Molecular and Cellular Endocrinology (2007Endocrinology ( ), doi:10.1016Endocrinology ( /j.mce.2008 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractCortistatin (CST) is a recently described neuropeptide that shares high homology with somatostatin (somatotropin release-inhibiting factor, SRIF) and binds with high affinity to all somatostatin receptor (sst) subtypes. CST is currently known to have a widespread distribution in many human organs including the immune system. The activities specific to CST may be partially attributable to its binding to the growth hormone secretagogue (GHS) receptor (GHS-R) and the orphan Gprotein-coupled receptor MrgX2. Human immune cells produce CST, whereas macrophage lineage and activated endothelium express sst 2 , and human lymphocytes express sst 3 . The human thymus expresses sst 1,2,3 , MrgX2 and almost all immune cells express GHS-R. Moreover, at this very moment promising research with CST in experimental animal models is being performed. On the basis of these promising results, studies aiming to further evaluate the possibilities of CST as a therapeutic agent in human immune mediated inflammatory diseases are warranted.

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“…In vitro, NPY was found to stimulate macrophage functions, including chemotaxis, in some studies but inhibited these responses in others (19,23,45,46). NPY was also found to inhibit the expression of costimulatory molecules on monocytes in a rat model of experimental autoimmune encephalitis (47).…”

Section: Discussionmentioning

confidence: 99%

“…NPY is also upregulated in the cerebrospinal fluid of patients with HIV encephalopathy, although the effect of this upregulation remains unknown (18). Recent studies with macrophage-like cell lines or isolated macrophages have demonstrated that NPY can influence macrophage activation (19)(20)(21)(22)(23)(24). Additionally, NPY has been found to inhibit interleukin 1␤ (IL-1␤)-induced activation of microglia (25,26), the primary resident myeloid cell type in the CNS.…”

mentioning

confidence: 99%

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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NEUROPEPTIDES MODULATE A MURINE MONOCYTE/MACROPHAGE CELL LINE CAPACITY FOR PHAGOCYTOSIS AND KILLING OFLEISHMANIA MAJORPARASITES

Cited by 42 publications

References 43 publications

Increased Susceptibility of Melanin-Concentrating Hormone-Deficient Mice to Infection with Salmonella enterica Serovar Typhimurium

Increased Susceptibility of Melanin-Concentrating Hormone-Deficient Mice to Infection with Salmonella enterica Serovar Typhimurium

The role of cortistatin in the human immune system

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

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