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At least 685 records · Page 38Linked to original sources
PubMed2002

Expression of functional kappa-opioid receptors on murine dendritic cells.

Endogenous and exogenous opioids are known to exert direct effects on the immune system and the expression of functional opioid receptors has been reported for several immune cell types. Since dendritic cells are important inducers and regulators of immune responses, we investigated whether murine dendritic cells express functional kappa-opioid receptors. FACScan analysis and radioligand binding studies revealed the expression of kappa-opioid receptors by murine dendritic cells, which by RT-PCR were also shown to express kappa-opioid mRNA. In a primary allogenic mixed-lymphocyte reaction the kappa-agonists dynorphin A and U50488H suppressed the capacity of dendritic cells to induce T-cell proliferation in a concentration-dependent manner. Preincubation with the kappa-specific antagonist nor-binaltrophimine abolished the observed effect, indicating specificity. In contrast, antigen uptake by dendritic cells as well as phenotypic maturation of dendritic cells were not influenced by the kappa-agonists dynorphin A and U50488H. In summary our data demonstrate that dendritic cells express functional kappa-opioid receptors and that specific agonists exert a direct effect on these cells. Therefore, dendritic cells might be involved in the interaction of the neuroendocrine hormones and the immune system.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed2002

Adrenergic nerve fibres and mast cells: correlation in rat thymus.

The interactions between adrenergic nerve fibres and mast cells (MCs) were studied in the thymus of adult and old rats by morphological methods and by quantitative analysis of images (QAIs). The whole thymus was drawn in adult (12 months old) rats: normal, sympathectomized or electrostimulated. Thymuses from the above-mentioned animals were weighed, measured and dissected. Thymic slices were stained with eosin orange for detection of microanatomical details and with Bodian's method for identification of the whole nerve fibres. Thymic MCs were stained with Astrablau. Histofluorescence microscopy was used for staining of adrenergic nerve fibres. Finally, all morphological results were submitted to the QAIs and statistical analysis of data. Our results suggest that after surgical sympathectomy, the greater part of adrenergic nerve fibres disappear while related MCs appear to show less evident fluorescence and few granules. On the contrary, electrostimulation of the cervical superior ganglion induced an increase in the fluorescence of adrenergic nerve fibres and of related MCs.

Adrenergic Fibers↗
PubMed2001

Embryonic "binge" cocaine exposure alters neural-immune and neural-endocrine interactions in young chickens: involvement of serotonin(2) receptors.

As part of our characterization of the developmental consequences of prenatal cocaine exposure, cocaine was injected into eggs containing viable chicken embryos on embryonic day (E) 18 and the fever response to the endotoxin lipopolysaccharide (LPS) and a delayed-type hypersensitivity response to phytohemagglutinin (PHA) were assessed postnatally. E18 cocaine exposure did not affect basal body temperature. LPS induced a fever in the chicks at 4 h post-injection on post-hatch day (D) 4 and 2 h post-injection on D24. E18 cocaine exposure suppressed the peak LPS-induced fever by 50% at both ages. E18 cocaine exposure also suppressed the hypersensitivity reaction to an intradermal injection of PHA on D17, while having no effect on the response to a saline injection. To determine the importance of serotonin(2) (5-HT(2)) receptors in the developmental toxicity of cocaine, varying doses of the 5-HT(2) antagonist ritanserin were injected on E17 followed by cocaine on E18. Ritanserin, like cocaine, did not alter basal temperature, but it dose-relatedly attenuated or blocked cocaine's effect on LPS-induced fever on both D4 and D24. Ritanserin pretreatment was also able to block the blunted isolation stress response seen in D16 chicks following E18 cocaine exposure. Thus, late prenatal cocaine exposure significantly alters adaptive fever and hypersensitivity responses, and embryonic 5-HT(2) receptors played a mediating role in the fever effect.

Animals↗
PubMed2001

Neonatal chlorpyrifos administration elicits deficits in immune function in adulthood: a neural effect?

Neural input plays a key role in the establishment of immune function, and environmental agents or drugs that interfere with the development of the nervous system elicit corresponding immunologic deficits. In the current study, we gave neonatal rats the widely used organophosphate pesticide, chlorpyrifos (CPF), and determined the immediate and long-term effects on T-lymphocyte function. Exposure of neonatal rats to 1 mg/kg of CPF daily on postnatal days (PN) 1-4 had no immediate effect (PN5) on T-cell mitogenic responses to concanavalin A challenge. However, once the animals reached adulthood, T-cell responses were significantly impaired. There were no deficits in basal T-cell replication rates, implying that the adverse effect of CPF exposure was specific to mitogenic activation. Treatment during a later neonatal period (PN11-14) elicited similar deficits in adulthood. CPF administration leads to inhibition of cholinesterase, and a cholinergic connection is supported by the fact that the results seen here correspond to those seen with a direct cholinergic stimulant (nicotine) administered during gestation or adolescence. These results indicate that exposure to CPF during a developmental period in which this organophosphate pesticide is known to produce lasting changes in neural function, elicits corresponding, long-term deficits in immune competence.

Age Factors↗
PubMed2000

Residual public repertoires to self.

The consensus view about the constitution of the T cell receptor repertoire has shifted greatly even during this decade. Although the discovery of autoimmunity in the fifties had clearly shown that a repertoire must exist directed against self antigens, the extent of this repertoire was not fully appreciated. In our work we have tried to elucidate the nature of the antigenic specificities against which this self-directed repertoire is directed. The non-tolerized (residual) self-directed repertoire is a direct consequence of the hierarchy of antigenic determinant display, and is the most important influence in the organism's choice of which T cells to delete. Certain determinants remain "silent" and are neither displayed in the thymus nor in the periphery: these are a heterogeneous group which are invisible to T cells for a variety of reasons. One reason relates to the processing and presentation of determinants, and a second derives from the nature of the T cell receptor (TcR) and the avidity of the T cell for its target specificity.

Animals↗
PubMed2000

Global immune disregulation in multiple sclerosis: from the adaptive response to the innate immunity.

Increasing evidences show a global immune disregulation in multiple sclerosis (MS). The possible involvement of myelin and non-myelin (auto-)antigens in the autoaggressive process as well as the disregulation of both adaptive and innate immunity challenge the concept of specific immunotherapy. T cells at the boundary between innate and adaptive immunity, whose immunoregulatory role is becoming increasingly clear, have recently been shown to bear relevance for MS pathogenesis. Global immune interventions (and type I interferons may be considered as such) aimed at interfering with both innate and acquired immune responses seem to be a most promising therapeutic option in MS.

Humans↗
PubMed2000

Evidence for a role of gammadelta T cells in demyelinating diseases as determined by activation states and responses to lipid antigens.

In this report we review current information on the phenotypic and functional properties of gammadelta T cells in demyelinating disorders. The results support the conclusion that although gammadelta T cells show evidence of activation in patients with either multiple sclerosis (MS) or Guillain Barrè syndrome (GBS), differences exist in the phenotypic and functional properties of these cells between the two diseases. In particular, our data indicate that in patients with MS the Vdelta2 subset is activated and that these cells can be induced to secrete high levels of proinflammatory cytokines. In contrast, in patients with GBS, the Vdelta1 subset is expanded and can be induced to secrete cytokines more associated with a humoral response.

Guillain-Barre Syndrome↗
PubMed2000

Genetics of rat neuroinflammation.

The definition of genes regulating the pathogenetic pathways of autoimmune neuroinflammation, may provide targets for new therapeutic strategies. This is not easily accomplished in human disease. Such genetic dissection can more readily be done by the use of inbred rodent strains. With these, genetic heterogeneity is avoided and variation in the environmental influences is minimized. Close mimicking of the human disease characteristics is desirable in such endeavors. Chronic relapsing experimental autoimmune encephalomyelitis (EAE) with MS-like histopathology is achieved after immunization of certain rat strains with myelin oligodendrocyte glycoprotein (MOG) or spinal cord homogenate. The major histocompatibility complex (MHC) regulate the ease by which the environmental trigger in the form of immunisation induces disease. Use of intra-MHC recombinant strains demonstrated major influences from the MHC class II genome region, but additional influences from both the MHC class I and III regions. These findings now provide a basis for studies of the mechanisms for MHC-controlled autoimmune pathogenicity leading to MS-like disease. Gene mapping of F2 crosses between susceptible and resistant rat strains demonstrated nine genome regions outside the MHC which regulate different phenotypes of rat EAE. Many of these co-localize with genome regions regulating other organ-specific disease such experimental arthritis, suggesting a sharing of disease pathways. Further finemapping can lead to the exact identification of disease regulating genes. Interestingly, we have also demonstrated a non-MHC gene control of the inflammatory response, in the form of glial cell activation, and neuronal degeneration, subsequent to anterior nerve root avulsion in rats. The genetic dissection of these influences may unravel pathways controlling CNS vulnerability.

Animals↗
PubMed2000

Glia-T cell dialogue.

Interactions of CD4(+) T helper (Th) cells with microglia and astrocytes are likely to play an important role in regulating immune responses as well as tissue damage and repair during infectious and autoimmune central nervous system (CNS) diseases. T cells secreting Th1-type cytokines provide inducing signals for microglia to mature into functional antigen presenting cells (APC). The ability of microglia to act as efficient APC for the restimulation of Th1 cells suggests a role for these cells in the local amplification of pro-inflammatory immune responses. Conversely, the Th2-inducing capacity of microglia and astrocytes together with their ability to produce anti-inflammatory mediators could play a role in providing counter-regulatory signals limiting CNS inflammation. In this article, we review recent studies addressing the functional significance of T cell-CNS glia interactions and present new data on the expression of cyclooxygenase-2, the inducible enzyme involved in prostanoid biosynthesis, in microglia and astrocytes during the course of experimental allergic encephalomyelitis.

Astrocytes↗
PubMed2000

Expression of metabotropic glutamate receptors in murine thymocytes and thymic stromal cells.

RT-PCR combined with immunoblotting showed the expression of group-I (mGlu1 and 5) and group-II (mGlu2 and 3) metabotropic glutamate receptors in whole mouse thymus, isolated thymocytes and TC-1S thymic stromal cell line. Cytofluorimetric analysis showed that mGlu-5 receptors were absent in CD4(-)/CD8(-) but present in more mature CD4(+) CD8(+) and CD4(+)CD8(-) thymocytes. mGlu-1a receptors showed an opposite pattern of expression with respect to mGlu5, whereas mGlu2/3 receptor expression did not differ between double negative and double positive cells. mGlu receptors expressed in both thymic cell components were functional, as indicated by measurements of polyphosphoinositide hydrolysis or cAMP formation. These data suggest a possible role for mGlu receptor signalling in the thymus.

Animals↗
PubMed2000

Inflammation is a component of neurodegeneration in response to Venezuelan equine encephalitis virus infection in mice.

Infection with the mosquito-transmitted Venezuelan equine encephalitis virus (VEE) causes an acute systemic febrile illness followed by meningoencephalitis. In this communication we characterize the cytokine profile induced in the central nervous system (CNS) in response to virulent or attenuated strains of VEE using RNase Protection Assays. Virulent VEE causes an upregulation of multiple pro-inflammatory genes including inducible nitric oxide synthase (iNOS) and tumor necrosis factor alpha (TNF-alpha). To determine if iNOS and TNF-alpha contribute to the neuropathogenesis of VEE infection, iNOS and TNF receptor knockout mice were used in VEE mortality studies and exhibited extended survival times. Finally, CNS tissue sections labeled for VEE antigen, and adjacent sections double-labeled for an astrocyte marker and apoptosis, revealed that apoptosis of neurons occurs not only in areas of the brain positive for VEE-antigen, but also in areas of astrogliosis. These findings suggest that the inflammatory response, which is in part mediated by iNOS and TNF-alpha, may contribute to neurodegeneration following encephalitic virus infection.

Animals↗
PubMed2000

Anti-tumor effect of L-deprenyl is associated with enhanced central and peripheral neurotransmission and immune reactivity in rats with carcinogen-induced mammary tumors.

L-Deprenyl, a monoamine oxidase-B (MAO-B) inhibitor, has previously been shown to improve immune responses and restore noradrenergic (NA) nerve fibers in the spleen of old rats. In tumor-bearing rats, L-deprenyl inhibited tumor incidence and enhanced tuberoinfundibular dopaminergic (TIDA) neurotransmission in the hypothalamus. The aim of the present study was to investigate whether alterations in sympathetic NA activity and cellular immune responses in the spleen, and TIDA activity in the hypothalamus, accompany deprenyl-induced regression of 9,10-dimethyl-1,2-benzanthracene (DMBA)-induced mammary tumors. Rats with DMBA-induced mammary tumors were treated with 0, 2.5 mg, or 5.0 mg/kg body weight of deprenyl daily for 13 weeks. Saline-treated tumor-bearing rats exhibited reduced splenic IL-2 and IFN-gamma levels, and lowered splenic norepinephrine (NE) concentration and hypothalamic dopaminergic activity, compared to rats without tumors. In contrast, treatment with 2.5 mg/kg and 5.0 mg/kg of deprenyl reduced the number and size of mammary tumors. Deprenyl-induced tumor regression was accompanied by increased immune measures in the spleen, including enhanced IL-2 and IFN-gamma production, and NK cell activity. Neural measures enhanced by deprenyl included NE concentration in the spleen and TIDA neuronal activity in the hypothalamus. These results suggest that (1) mammary tumorigenesis is associated with the inhibition of sympathetic NA activity in the spleen, TIDA activity in the hypothalamus, and cell-mediated immunity, and (2) reversal of the inhibition of catecholaminergic neuronal activities of the central nervous system and peripheral nervous system by deprenyl may enhance anti-tumor immunity.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2000

Role of MIP-1beta and RANTES in HIV-1 infection of microglia: inhibition of infection and induction by IFNbeta.

Microglia are the major target of HIV-1 infection in the brain. Microglial infection is CD4-dependent, but the role of chemokine receptors CCR5 and CCR3 and their natural ligands in modulating HIV-1 infection in microglia has been questioned. In primary human fetal microglial cultures, we demonstrate that HIV-1 infection of these cells is dependent on CCR5, since an antibody to CCR5 completely blocked productive infection. Anti-CCR3, in contrast, had a smaller inhibitory effect which was not statistically significant. The chemokine ligands for CCR5, RANTES and MIP-1beta, also potently inhibited HIV-1 infection in microglia, but the third ligand MIP-1alpha failed to show inhibition. Interestingly, when microglial cultures were treated with antibodies specific to each of these chemokines, HIV-1 infection was enhanced by anti-RANTES and anti-MIP-1beta, but not by anti-MIP-1alpha. These results demonstrate the presence of endogenous chemokines that act as endogenous inhibitors of HIV-1 infection in microglia. Additionally, IFNbeta, a known anti-viral cytokine, also provided potent inhibition of viral infection as well as induction of all three chemokines in microglia. These results suggest the possibility that type I interferon can down-modulate microglial HIV-1 infection in vivo by multiple mechanisms.

AIDS Dementia Complex↗
PubMed2000

Interleukin 1 receptor accessory protein (IL-1RAcP) is necessary for centrally mediated neuroendocrine and immune responses to IL-1beta.

Mice deficient for the IL-1RAcP gene (IL-1RAcP KO) were used to explore the role of IL-1RAcP in physiological functions of brain IL-1beta. Animals were injected i.c.v. with two different doses of recombinant human (rh) IL-1beta: a small one (750 pg) known to induce sickness behavior, and a larger one (50 ng), chosen to counteract the possible loss of affinity of IL-1beta on its receptor. Neuroendocrine and immune parameters were measured 2 h after IL-1 injection. The increase of plasma corticosterone induced by rhIL-1beta in wild-type (WT) mice was not observed in IL-1RAcP KO mice. Likewise, the depression of splenocyte proliferation occurred in WT but not in KO mice. Finally, in opposition to WT mice, plasma levels and brain cortical content of IL-6 in IL-1RAcP KO mice remained unchanged as compared to saline-injected controls. The results clearly demonstrate that IL-1RAcP is necessary for the induction of the main neuroendocrine and immune effects of central IL-1beta.

Animals↗
PubMed2000

Altered beta-adrenoceptor function associated to protein kinase C activation in hyperproliferative T lymphocytes.

beta-Adrenoceptor (betaAR) expression and function as well as its modulation via intracellular transduction signals, were analyzed on the T cell lymphoma BW5147. Independently to the kinetic of proliferation and relative to the number of receptors displayed in normal T lymphocytes, BW5147 cells displayed a decreased number of betaAR, uncoupled to adenylate cyclase, but coupled to protein kinase C stimulation. This last effect was impaired by a beta-antagonist and by blockers of the enzymatic pathways involved in T lymphocyte proliferation, inducing a recovery of betaAR sites. Down-regulation of betaAR would implicate the loss of a negative neuroimmune control mechanism for lymphocyte proliferation. The coupling of the remaining sites to a positive signal for cellular activation, would contribute to establish an hyperproliferative state.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2000

Mechanisms underlying chemical sympathectomy-induced suppression of herpes simplex virus-specific cytotoxic T lymphocyte activation and function.

Lymphoid tissues are extensively innervated by noradrenergic fibers of the sympathetic nervous system. 6-hydroxydopamine (6-OHDA)-induced chemical sympathectomy is commonly used to assess the impact of this innervation on immune function. Using the glucocorticoid receptor antagonist RU486, the mineralocorticoid receptor antagonist spironolactone, and the beta-adrenergic receptor antagonist nadolol, the roles of corticosterone and norepinephrine in sympathectomy-mediated modulation of both the primary and memory cellular immune responses to herpes simplex virus type 1 (HSV-1) infection was investigated. We demonstrated that both of these immunomodulators play a role in mediating sympathectomy-induced suppression of the generation of HSV-specific primary cytotoxic T lymphocytes (CTL) and the activation of HSV-specific memory CTL (CTLm). Furthermore, we demonstrated a role for both Type I and Type II corticosteroid receptors in the regulation of HSV-specific immunity. Overall, these findings not only further support a role for neuroendocrine-mediated modulation of immune function, but also a need to exercise caution in attributing the effects of chemical sympathectomy to solely the absence of sympathetic innervation of lymphoid tissues.

Animals↗
PubMed2000

Vasoactive intestinal peptide and pituitary adenylate cyclase activating polypeptide inhibit the MEKK1/MEK4/JNK signaling pathway in LPS-stimulated macrophages.

The vasoactive intestinal peptide (VIP) and the pituitary adenylate cyclase activating polypeptide (PACAP), two immunomodulatory neuropeptides that affect both innate and acquired immunity, downregulate TNFalpha expression in LPS-stimulated peritoneal macrophages and Raw 264.7 cells. We showed previously that VIP/PACAP change the composition of the CRE-binding complex in the TNFalpha promoter from highc-Jun/(low)CREB, characteristic for LPS-stimulated macrophages, to lowc-Jun/(high)CREB, characteristic for the unstimulated cells. In the present study we examined the effects of VIP/PACAP on the MEKK1/MEK4/JNK transduction pathway, and on the subsequent changes in Jun family members. Our studies indicate that VIP/PACAP inhibit MEKK1 activity, and the subsequent phosphorylation of MEK4, JNK, and c-Jun. Treatment with VIP or PACAP results in a decrease in AP-1 binding, and a marked change in the composition of the AP-1 complexes from c-Jun/c-Fos to JunB/c-Fos. Western blots confirm that VIP stimulates JunB production in LPS-stimulated macrophages. Both the inhibition of the MEKK1/MEK4/JNK pathway, leading to the reduction in phosphorylated c-Jun, and the stimulation of JunB, are mediated through the specific VPAC1 receptor and the cAMP/PKA pathway. The VIP/PACAP interference with the stress-induced SAPK/JNK pathway in stimulated macrophages may represent a significant element in the regulation of the inflammatory response by the endogenous neuropeptides.

Animals↗