Neurokinin A engages neurokinin-1 receptor to induce NF-κB-dependent gene expression in murine macrophages: implications of ERK1/2 and PI 3-kinase/Akt pathways

Sun, Jia; Ramnath, Raina Devi; Tamizhselvi, Ramasamy; Bhatia, Madhav

doi:10.1152/ajpcell.00042.2008

Cited by 25 publications

(27 citation statements)

References 51 publications

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“…In this respect, Sun et al (2008) describe the upregulation of chemokine and cytokine receptor expression by SP in neutrophils, an effect involving NK-1R and the activation of NF-jB. These findings, in accordance with ours, suggest and that SP is related to chronic inflammation with regulation of the production of LTB 4 .…”

Section: Discussionsupporting

confidence: 89%

Substance P Upregulates LTB4 in Rat Adherent Macrophages from Granuloma Induced by KMnO4

et al. 2009

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Substance P (SP) is an important neuropeptide involved in neurogenic inflammation and most of its pathophysiological functions are mediated through binding to the neurokinin-1 receptor. SP exerts various proinflammatory actions on immune-cells, including macrophages. Several compounds such as cytokines have the capacity to activate and stimulate macrophages to produce arachidonic acid oxygenation and lipoxygenation products. Leukotriene B4 (LTB4) is one of the most important mediators of leukocyte activation in acute and chronic inflammatory reactions. LTB4 stimulates chemotaxis, lysosomal enzyme release, and cell aggregation. In this report, we studied the effect of SP on rat adherent granuloma macrophages (RAGMs). The chronic granuloma in rat was induced by dorsal injections of a potassium permanganate (KMnO4) saturated crystal solution (200 microl of a 1:40 dilution). After 7 days, all rats developed a subcutaneous granuloma in the injection site from which infiltrated macrophages were extracted, isolated, and cultured in vitro. We tested the hypothesis that SP stimulates the production of LTB4 in RAGMs and increases lipoxygenase expression. Here we show that the cell-free supernatant of RAGMs stimulated with SP (10 microM), resulted in statistically significant increases of LTB4 Preincubation of RAGMs with NDGA (nordihydroguaiaretic acid (10 microM), completely abolished the production of LTB(4) in the supernatants and lipoxygenase expression on RAGMs challenged with SP, or the cation ionophore A23187 (positive control). Similar effects were obtained when the cells were pretreated with dexamethasone (10 microM). Our results suggest that SP is able to stimulate the release of LTB4 and lipoxygenase expression in macrophages from chronic inflammatory granuloma and provide further evidence for a neuroinflammatory pathway.

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Section: Discussionsupporting

confidence: 89%

Substance P Upregulates LTB4 in Rat Adherent Macrophages from Granuloma Induced by KMnO4

et al. 2009

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“…The findings strongly suggest that the SP-NK1R-signaling cascade contributes to type 1 immunity, as well as inflammatory responses. Although NK1R is ubiquitously expressed in addition to the CNS, it was demonstrated that NK2R is mostly expressed in peripheral tissues (29)(30)(31)(32)(33). Although the precise function of the NKA-NK2R-signaling pathway, especially in immune responses, is less-well known compared with that of NK1R, we demonstrated in this study that NK2R-mediated NKA stimulation enhances DC function, such as IFN-a/b production (Fig.…”

Section: Discussionmentioning

confidence: 55%

“…Although the tachykinins were initially considered neurotransmitters, many articles reported that expression of their receptors, NK1R and NK2R, was observed in nonneural tissues, including endothelial cells, fibroblasts, smooth muscle cells, and inflammatory cells, suggesting that tachykinins function between the nervous system and other organs (27)(28)(29)(30)(31)(32)(33).…”

Section: Discussionmentioning

confidence: 99%

Neuropeptide Signaling Activates Dendritic Cell-Mediated Type 1 Immune Responses through Neurokinin-2 Receptor

Kitamura

Kobayashi

Wakita

et al. 2012

The Journal of Immunology

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Neurokinin A (NKA), a neurotransmitter distributed in the central and peripheral nervous system, strictly controls vital responses, such as airway contraction, by intracellular signaling through neurokinin-2 receptor (NK2R). However, the function of NKA–NK2R signaling on involvement in immune responses is less-well defined. We demonstrate that NK2R-mediated neuropeptide signaling activates dendritic cell (DC)-mediated type 1 immune responses. IFN-γ stimulation significantly induced NK2R mRNA and remarkably enhanced surface protein expression levels of bone marrow-derived DCs. In addition, the DC-mediated NKA production level was significantly elevated after IFN-γ stimulation in vivo and in vitro. We found that NKA treatment induced type 1 IFN mRNA expressions in DCs. Transduction of NK2R into DCs augmented the expression level of surface MHC class II and promoted Ag-specific IL-2 production by CD4+ T cells after NKA stimulation. Furthermore, blockade of NK2R by an antagonist significantly suppressed IFN-γ production by both CD4+ T and CD8+ T cells stimulated with the Ag-loaded DCs. Finally, we confirmed that stimulation with IFN-γ or TLR3 ligand (polyinosinic-polycytidylic acid) significantly induced both NK2R mRNA and surface protein expression of human PBMC-derived DCs, as well as enhanced human TAC1 mRNA, which encodes NKA and Substance P. Thus, these findings indicate that NK2R-dependent neuropeptide signaling regulates Ag-specific T cell responses via activation of DC function, suggesting that the NKA–NK2R cascade would be a promising target in chronic inflammation caused by excessive type 1-dominant immunity.

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“…The activation of NF-κB is also regulated by upstream signaling proteins including MAPKs (ERK, JNK, and p38 MAPK) and Akt, those are groups of signaling molecules to play pivotal roles in NF-κB activation [13,27]. MAPKs are involved in pro-inflammatory signaling cascades and regulate the activation of NF-κB in LPS-stimulated immune cells [2,3,25].…”

Section: Discussionmentioning

confidence: 99%

Anti-inflammatory effects of phlorofucofuroeckol B-rich ethyl acetate fraction obtained from Myagropsis myagroides on lipopolysaccharide-stimulated RAW 264.7 cells and mouse edema

Joung¹,

Lee²,

Choi³

et al. 2012

International Immunopharmacology

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Neurokinin A engages neurokinin-1 receptor to induce NF-κB-dependent gene expression in murine macrophages: implications of ERK1/2 and PI 3-kinase/Akt pathways

Abstract: Sun J, Ramnath RD, Tamizhselvi R, Bhatia M. Neurokinin A engages neurokinin-1 receptor to induce NF-B-dependent gene expression in murine macrophages: implications of ERK1/2 and PI 3-kinase/Akt pathways.

Cited by 25 publications

References 51 publications

Substance P Upregulates LTB4 in Rat Adherent Macrophages from Granuloma Induced by KMnO4

Substance P Upregulates LTB4 in Rat Adherent Macrophages from Granuloma Induced by KMnO4

Neuropeptide Signaling Activates Dendritic Cell-Mediated Type 1 Immune Responses through Neurokinin-2 Receptor

Anti-inflammatory effects of phlorofucofuroeckol B-rich ethyl acetate fraction obtained from Myagropsis myagroides on lipopolysaccharide-stimulated RAW 264.7 cells and mouse edema

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