Neurokinin 1 receptor isoforms and the control of innate immunity.
ABSTRACT Substance P is the prototype tachykinin peptide and triggers a variety of biological effects in both the nervous and immune system. Two naturally occurring variants of the neurokinin 1 receptor (NK1R) mediate the effects of SP: a 'classic' full-length receptor and a truncated (tail-less) form that lacks 96 amino acid residues at the C-terminus. Most research has focused on the full length receptor and the truncated NK1R has not been extensively explored. Recent data demonstrate that truncated NK1R has important functional roles, including modulation of responses triggered by cytokines, chemotaxis of macrophages and regulation of HIV replication. Targeting the truncated NK1R with pharmacologic agents might result in novel therapeutic approaches in diseases which affect the immune system, including HIV disease.
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ABSTRACT: In the last few years, a substantial body of evidence indicates that cutaneous psoriasis and psoriatic arthritis patients are at higher risk of developing cardiovascular disease. However, underlaying mechanism remains no completed understood. In this review we discuss the role of the immune system in the development of atherosclerosis, focusing on available data implicating the role of an enhanced immune-mediated pro-inflammatory status in psoriasis and psoriatic arthritis diseases.01/2015; 24. DOI:10.1016/j.ijcme.2015.01.005
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ABSTRACT: Pain is a serious problem for infants and children and treatment options are limited. Moreover, infants born prematurely or hospitalized for illness likely have concurrent infection that activates the immune system. It is now recognized that the immune system in general and glia in particular influence neurotransmission and that the neural bases of pain are intimately connected to immune function. We know that injuries that induce pain activate immune function and suppressing the immune system alleviates pain. Despite this advance in our understanding, virtually nothing is known of the role that the immune system plays in pain processing in infants and children, even though pain is a serious clinical issue in pediatric medicine. This brief review summarizes the existing data on immune-neural interactions in infants, providing evidence for the immaturity of these interactions. © 2014 Wiley Periodicals, Inc. Dev Psychobiol.Developmental Psychobiology 06/2014; 56(8). DOI:10.1002/dev.21229 · 3.16 Impact Factor
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ABSTRACT: Despite the fact that glucocorticoids and long acting beta agonists are effective treatments for asthma, their effects on human mast cells (MC) appear to be modest. Although MC are one of the major effector cells in the underlying inflammatory reactions associated with asthma, their regulation by these drugs is not yet fully understood and, in some cases, controversial. Using a human immortalized MC line (LAD2), we studied the effects of fluticasone propionate (FP) and salmeterol (SM), on the release of early and late phase mediators. LAD2 cells were pretreated with FP (100 nM), SM (1 µM), alone and in combination, at various incubation times and subsequently stimulated with agonists substance P, C3a and IgE/anti-IgE. Degranulation was measured by the release of β-hexosaminidase. Cytokine and chemokine expression were measured using quantitative PCR, ELISA and cytometric bead array (CBA) assays. The combination of FP and SM synergistically inhibited degranulation of MC stimulated with substance P (33% inhibition compared to control, n = 3, P<.05). Degranulation was inhibited by FP alone, but not SM, when MC were stimulated with C3a (48% inhibition, n = 3, P<.05). As previously reported, FP and SM did not inhibit degranulation when MC were stimulated with IgE/anti-IgE. FP and SM in combination inhibited substance P-induced release of tumor necrosis factor (TNF), CCL2, and CXCL8 (98%, 99% and 92% inhibition, respectively, n = 4, P<.05). Fluticasone and salmeterol synergistically inhibited mediator production by human MC stimulated with the neuropeptide substance P. This synergistic effect on mast cell signaling may be relevant to the therapeutic benefit of combination therapy in asthma.PLoS ONE 05/2014; 9(5):e96891. DOI:10.1371/journal.pone.0096891 · 3.53 Impact FactorThis article is viewable in ResearchGate's enriched formatRG Format enables you to read in context with side-by-side figures, citations, and feedback from experts in your field.