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At least 721 records · Page 40Linked to original sources
PubMed2002

Production and secretion of calcitonin gene-related peptide from human lymphocytes.

Calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide, which is mainly present in primary sensory nerves. Although our previous study has shown that rat lymphocytes can synthesize beta-CGRP, there is no evidence demonstrating whether CGRP can be synthesized by human lymphocytes. In this study, the production of CGRP from human lymphocytes from spleen and blood were investigated by using CGRP-specific radioimmunoassay (RIA), and RNase protection assay (RPA). The results showed that human T lymphocyte mitogen, such as phytohemagglutinin (PHA), could time- and dose-dependently induce hCGRP secretion; rhIL-2 alone did not effect hCGRP secretion, but it could potentiate PHA-evoked hCGRP secretion from human spleen lymphocytes. RPA showed that alpha- and beta-CGRP mRNA were both constitutively expressed in unstimulated human peripheral blood mononuclear cells (PBMC). PHA could cause beta-hCGRP but not alpha-hCGRP mRNA increase in a time-dependent manner. In addition, hCGRP(8-37), a CGRP(1) receptor antagonist, enhanced PHA or human interleukin-2 (rhIL-2), induced the proliferation of splenocytes and PBMC. These results suggest that hCGRP is produced and secreted by human lymphocyte. Lymphocyte mitogen can induce the elevation of beta-CGRP synthesis and secretion. The lymphocyte-derived beta-CGRP may inhibit, at least in part, lymphocytes proliferation, which are then involved in the modulation of human T lymphocyte function in response to immune stimulation.

Calcitonin Gene-Related Peptide↗
PubMed2002

Nitric oxide synthase I and VIP-activated signaling are affected in salivary glands of NOD mice.

The autoimmune sialadenitis developed by non-obese diabetic (NOD) mice is considered a suitable model to study the ethiopathogenic mechanisms leading to sicca symptoms in Sjögren's syndrome (SS). Evidence supporting a neural rather than immune origin of the secretory dysfunction has been provided. As both nitric oxide and vasoactive intestinal peptide (VIP) are common messengers to nervous and immune systems mediating secretory and inflammatory responses, we examined nitric oxide synthase (NOS) activity with special focus on VIP-mediated effects in salivary glands of NOD mice. We found a decreased NOS activity and expression in major salivary glands of NOD mice with respect to control mice. In addition, there was a deficient VIP-activated signaling associated with a reduced saliva and amylase secretion in response to VIP. Our results support the hypothesis of an impaired balance of neuroimmune interactions in salivary glands as early events to take place in the progressive loss of secretory function of NOD mice.

Age Factors↗
PubMed2002

The new orally active immunoregulator laquinimod (ABR-215062) effectively inhibits development and relapses of experimental autoimmune encephalomyelitis.

A new orally active drug, laquinimod (ABR-215062), was shown to completely inhibit the development of murine acute experimental autoimmune encephalomyelitis (EAE). Furthermore, leukocyte infiltration into the central nervous system (CNS) was abolished in the laquinimod-treated animals. By direct comparison based on dose and total exposure, laquinimod was approximately 20 times more potent than the immunomodulator roquinimex. Laquinimod also had clear therapeutic effect when given after clinical onset in a chronic relapsing EAE model. It therefore represents a new orally active immunoregulatory drug without general immunosuppressive properties for the treatment of the autoimmune disease multiple sclerosis.

Adjuvants, Immunologic↗
PubMed2002

Behaviorally conditioned immunosuppression in the rat is regulated via noradrenaline and beta-adrenoceptors.

Using Cyclosporin A (CsA) as an unconditioned stimulus has previously demonstrated that behaviorally conditioned inhibition of splenocyte proliferation and cytokine production is mediated via the splenic nerve. Therefore, we currently examined the adrenergic modulation of conditioned suppression of splenocyte function. Chemical sympathectomy via 6-OHDA completely blocked the conditioned suppression of splenocyte proliferation to mitogens and cytokine (IL-2, IFN-gamma) production. Furthermore, administration of beta-adrenoceptor antagonist propranolol abrogated the conditioned effect on splenocyte proliferation. Supporting the position that conditioning is beta-adrenergic-dependent, addition of beta-adrenoceptor agonist, but not alpha-adrenoceptor agonists, to splenocytes in vitro mimicked the conditioned suppression of splenocyte functions, with these effects blocked by propranolol. Therefore, these data indicate that behavioral conditioning of splenocyte function in the rat is regulated by the sympathetic nervous system, predominantly via beta-adrenergic mechanisms.

Adrenergic beta-Agonists↗
PubMed2002

Induced neuronal expression of class I major histocompatibility complex mRNA in acute and chronic inflammation models.

Studies have demonstrated neuronal expression of class I major histocompatibility complex (MHC) mRNA and protein in normal and developing brain and in response to injury or viral infection. We report neuronal expression of class I MHC mRNA in hypothalamic paraventricular nucleus (PVN) neurons in rats following systemic infection with Trypanosoma brucei brucei parasites (chronic) and in response to intravenous 1 mg/kg lipopolysaccharide administration (acute peripheral) and in striatal neurons following intrastriatal 5 microg lipopolysaccharide injection (acute central). These results demonstrate that neurons can be a source of immune signaling molecules and establish class I MHC as part of the neuronal component of immune responses.

Acute Disease↗
PubMed2002

Peripheral protein immunization induces rapid activation of the CNS, as measured by c-Fos expression.

To investigate immune-to-brain communication, we challenged rats intraperitoneally with a protein antigen (keyhole limpet hemocyanin, KLH), and measured c-Fos expression in different brain structures. We found a rapid c-Fos expression 120 min after immunization in brain stem and forebrain structures, using a dose of KLH not inducing fever or malaise. Using proper controls, we found that this central response is related to the immunogenicity of the antigen and the magnitude of the immune response. Our results suggest that different interconnected brain cell groups respond rapidly to an immune challenge in the periphery, constituting an afferent pathway of neuroimmune communication.

Animals↗
PubMed2002

Stress-related modulation of matrix metalloproteinase expression.

Matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs), whose expression can be controlled by cytokines, play a role in extracellular matrix remodeling in physiological and pathological processes. Using a blister chamber wound model on UV-B-exposed human forearm skin, we examined whether stress or mood-associated neuroendocrine alteration is sufficient to modulate MMP and TIMP expression. We did not find evidence that depressive symptoms were reliably associated with modulation of either MMP or TIMP expression. However, we did find that activation of the hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenal medullary (SAM) axes can modulate levels of MMPs. A positive association between plasma norepinephrine levels and MMP-2 protein levels, and a negative correlation between plasma cortisol levels and MMP-2 levels were found. The data suggest that activation of the HPA and SAM axes, even in individuals within the normal range of depressive symptoms, could mediate MMP levels and wound healing in blister wounds.

Adrenal Medulla↗
PubMed2002

Maternal deprivation of rat pups increases clinical symptoms of experimental autoimmune encephalomyelitis at adult age.

Maternal deprivation of neonatal animals has been shown to induce long-lasting changes in the reactivity of the neuroendocrine system. The aim of the present study was to investigate whether maternal deprivation also affects susceptibility to immune-mediated diseases such as experimental autoimmune encephalomyelitis (EAE) in adult life. To this end, 9-day-old rat pups were subjected to a short-lasting maternal deprivation for a period of 24 h. At the age of 8 weeks, we induced EAE in these rats by immunization with myelin basic protein (MBP) in complete Freund's adjuvant. Our data demonstrate that short-lasting maternal deprivation induces a marked increase in the severity of EAE in the animals in later life. The histopathological evaluation of spinal cord and cerebellum corresponded with the observed differences in clinical symptoms of EAE. Moreover, neonatal maternal deprivation affects macrophage functioning at adult age. In contrast, no differences were observed in in vitro mitogen- and MBP-induced cytokine production by splenocytes. LPS-induced corticosterone release did not differ either between maternally deprived and control animals. We conclude that short-lasting neonatal maternal deprivation of rat pups has long-lasting consequences for macrophage activity and for susceptibility to the inflammatory autoimmune disease EAE.

Aging↗
PubMed2002

Cytokines and neuro-immune-endocrine interactions: a role for the hypothalamic-pituitary-adrenal revolving axis.

Cytokines, peptide hormones and neurotransmitters, as well as their receptors/ligands, are endogenous to the brain, endocrine and immune systems. These shared ligands and receptors are used as a common chemical language for communication within and between the immune and neuroendocrine systems. Such communication suggests an immunoregulatory role for the brain and a sensory function for the immune system. Interplay between the immune, nervous and endocrine systems is most commonly associated with the pronounced effects of stress on immunity. The hypothalamic-pituitary-adrenal (HPA) axis is the key player in stress responses; it is well established that both external and internal stressors activate the HPA axis. Cytokines are chemical messengers that stimulate the HPA axis when the body is under stress or experiencing an infection. This review discusses current knowledge of cytokine signaling pathways in neuro-immune-endocrine interactions as viewed through the triplet HPA axis. In addition, we elaborate on HPA/cytokine interactions in oxidative stress within the context of nuclear factor-kappaB transcriptional regulation and the role of oxidative markers and related gaseous transmitters.

Animals↗
PubMed2002

Catecholamine production and tyrosine hydroxylase expression in peripheral blood mononuclear cells from multiple sclerosis patients: effect of cell stimulation and possible relevance for activation-induced apoptosis.

Sympathoadrenergic mechanisms may play a role in multiple sclerosis (MS). We examined catecholamine (CA) levels and production and tyrosine hydroxylase (TH) expression in peripheral blood mononuclear cells (PBMCs) from MS patients, and the correlation between CA production and apoptosis in PBMCs. PBMCs from MS patients had increased norepinephrine (NE) levels. However, phytohaemagglutinin (PHA)-stimulated PBMCs from MS patients with active disease synthesized less dopamine (DA) than cells from both healthy controls and patients with inactive disease. PBMCs from patients with inactive disease showed lower expression of TH. Pharmacological inhibition of TH in cultured PBMCs stimulated with PHA reduced the percentage of apoptotic cells. Since a failure of activation-induced apoptosis in immune cells may be involved in MS, it is suggested that altered CA production by PBMCs may be implicated in such dysregulation.

Adult↗
PubMed2003

Galanin down-regulates microglial tumor necrosis factor-alpha production by a post-transcriptional mechanism.

The neuropeptide galanin (GAL) is up-regulated following neuronal axotomy or inflammation. Since other neuropeptides act as immunomodulatory agents, we sought to determine whether GAL might affect the murine microglial cell line BV2, which expresses the GAL2 receptor. Even at very low concentrations, GAL inhibited tumor necrosis factor-alpha (TNF alpha) release but not TNF alpha mRNA levels in LPS-stimulated BV2 cells. Northern blot analysis showed that GAL inhibited the addition of a poly(A) tail, and stability assays showed that it also destabilized TNF alpha mRNA. Thus, GAL inhibits TNF alpha production by a post-transcriptional mechanism that both prevents the efficient addition of the poly(A) tail and accelerates TNF alpha mRNA degradation.

Alzheimer Disease↗
PubMed2003

Expression of AMPA-type glutamate receptors in HEK cells and cerebellar granule neurons impairs CXCL2-mediated chemotaxis.

We find that cerebellar granule neurons (CGN) obtained from newborn rats (p3) migrate in response to both CXC chemokine ligand-2 (CXCL2) and -12 (CXCL12), while CGN from p7 rats are unresponsive to CXCL2. The expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-type glutamate receptor 1 (GluR1) greatly impairs the chemotaxis induced by CXCL2 in CXCR2-expressing HEK cells. By immunoprecipitation, we show that CXCR2 is associated with AMPA receptors (AMPARs) in p7 CGN, and with GluR1 co-expressed in HEK cells. Taken together, these results suggest that the association between CXCR2 and AMPARs results in the inhibition of CXCL2-dependent chemotaxis, and may represent a molecular mechanism underlying the modulation of nerve cell migration.

Age Factors↗
PubMed2003

Enhanced humoral response in kappa-opioid receptor knockout mice.

Opiates are major analgesics and addictive drugs described also as immunomodulators. Here, we investigated the contribution of kappa-opioid receptor (KOR) activity in immunity in vivo by studying immune responses in KOR knockout mice. These animals displayed a modest reduction in thymus cellularity and CD4(+) cell ratio, parallel to a slight increase in immature CD4(+)CD8(+) lymphocytes. In spleen, KOR null animals showed augmented cell number with no change in cell distribution. T and B lymphocyte proliferative capabilities in vitro, Natural Killer activity and steady-state Ig levels were unchanged in KOR-/- mice. We immunized the mice with the antigen keyhole limpet hemocyanin (KLH). Compared to wild-type (WT) mice, KOR-/- animals produced significant higher levels of antigen-specific total Ig, IgM, IgG1 and IgG2a antibodies. This enhancement of humoral activity was not observed in mu-opioid receptor and delta-opioid receptor knockout animals. These results show that endogenous activation of kappa-opioid receptors may exert a tonic inhibition of antibody (Ab) response.

Animals↗
PubMed2003

Differential expression of class I MHC mRNA in the hypothalamus of Lewis and Fischer rats.

The expression of class I major histocompatibility complex (MHC) mRNA was compared in the brains of inflammatory susceptible, hypothalamic-pituitary-adrenal (HPA)-axis blunted Lewis rats and inflammatory resistant, HPA-axis hyperresponsive Fischer rats by quantitative in situ hybridization following lipopolysaccharide (LPS) or vehicle administration. Lewis rats showed lower levels of class I MHC in the hypothalamic paraventricular nucleus (PVN) and retrochiasmatic area (RCA) compared to Fischer rats under both vehicle and LPS conditions. No differences were detected in other brain structures. Differential class I MHC expression in Lewis rats suggests an alteration in mechanisms related to cellular activity of neuroendocrine cells rather than alterations specific to neuroendocrine molecules.

Animals↗
PubMed2003

Relevance of neuropeptide Y for the neuroimmune crosstalk.

Both cellular and humoral functions of the immune system are modulated by the sympathetic nervous system (SNS). This interaction is mainly mediated by the release of catecholamines (CA) and their receptor-specific action on immune cells. However, neuropeptide Y (NPY), also present in sympathetic nerve terminals, is released upon SNS-stimulation. NPY modulates potent immunological effects in vitro and in vivo, such as differentiation of T helper cells, monocyte mediator release, NK cell activation, and immune cell redistribution. In addition to this direct action within the neuroimmune crosstalk, NPY is also able to modulate the immunomodulatory effects of other neurotransmitters, thereby acting as a neuroimmune co-transmitter. This review will discuss key findings from recent studies, provide implications for the clinical situation, and integrate the pleiotropic functions of NPY in the context of neuroimmune interactions.

Animals↗
PubMed2003

Effects of glossopharyngeal nerve transection on central and peripheral cytokines and serum corticosterone induced by localized inflammation.

Bilateral transection of the glossopharyngeal nerves (GLOx) disrupts the immune-to-brain communication from the posterior oral cavity. The current report tested whether this effect is due to the afferent (sensory) or efferent (parasympathetic motor) components of the nerve. Injection of lipopolysaccharide (LPS) into the soft palate (ISP) of GLOx or sham-operated (SHAM) rats increased the circulating levels of interleukin-1beta (IL-1beta), interleukin-1 receptor antagonist (IL-1ra) and corticosterone (CORT), as well the hypothalamic content of IL-1beta; no difference in circulating levels and hypothalamic content was found between GLOx and SHAM at 2 and 4.5 h after LPS injection. These results indicate that glossopharyngeal neural efferents do not mediate the effects of GLOx on the immune-to-brain communication.

Afferent Pathways↗
PubMed2003

The role of the sympathetic nervous system in moxibustion-induced immunomodulation in rats.

The effects of chemical sympathectomy on moxibustion-induced changes in splenic natural killer (NK) cell cytotoxicity, T and B cell proliferation were studied. Direct moxibustion was applied to the unilateral Zusanli region. NK cell cytotoxicity was suppressed by moxibustion in both vehicle-treated rats and sympathectomized rats. T cell proliferation was not affected by moxibustion. B cell proliferation showed no significant change in vehicle-treated rats, but an increase was seen in sympathectomized rats treated with moxibustion. Sympathectomy alone induced an augmentation of NK cell cytotoxicity and a suppression of T cell proliferation. These results suggest that the sympathetic nervous system (SNS) has no significant role in the mechanism of moxibustion-induced immunomodulation.

Animals↗