Preferential expression of the vasoactive intestinal peptide (VIP) receptor VPAC1 in human cord blood-derived CD34+CD38− cells: possible role of VIP as a growth-promoting factor for hematopoietic stem/progenitor cells

Kawakami, Manabu; Kimura, Takafumi; Kishimoto, Yasushi; Tatekawa, Toyoshi; Baba, Yoshifumi; Nishizaki, Takamichi; Matsuzaki, Noboru; Taniguchi, Yoshihiro; Yoshihara, Satoshi; Ikegame, Kazuhiro; Shirakata, Toshiaki; Nishida, Shinji; Masuda, Takayuki; Hosen, Naoki; Tsuboi, Akihiro; Oji, Yusuke; Oka, Y.; Ogawa, Hiroyasu; Sonoda, Yoshiaki; Sugiyama, Haruo; Kawase, Ichiro; Soma, Toshihiro

doi:10.1038/sj.leu.2403330

Cited by 17 publications

(15 citation statements)

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“…Monocytes and T cells also constitutively express VPAC 1 , whereas VPAC 2 is inducible by specific cell activation (35)(36)(37). VPAC 1 receptor has also been preferentially detected in CD34ϩ,CD38Ϫ primitive hematopoietic stem cells (38). All of these data indicated that in several systems, VPAC 2 could represent a marker of cell activation or differentiation, explaining its predominant presence in RA FLS or TNF␣-treated OA FLS.…”

Section: Discussionmentioning

confidence: 89%

Differential expression of vasoactive intestinal peptide and its functional receptors in human osteoarthritic and rheumatoid synovial fibroblasts

Juarranz

Gutiérrez‐Cañas

Santiago

et al. 2008

Arthritis & Rheumatism

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Objective. Vasoactive intestinal peptide (VIP) hasshown potent antiinflammatory effects in murine arthritis and ex vivo in human rheumatoid arthritis (RA) synovial cells. To investigate the potential endogenous participation of this system in the pathogenesis of RA, we analyzed the expression and regulation of VIP and its functional receptors in human fibroblast-like synoviocytes (FLS) from patients with osteoarthritis (OA) and patients with RA.Methods. The expression of VIP was studied by reverse transcription-polymerase chain reaction (RT-PCR), enzyme immunoassay, and immunofluorescence in cultured FLS, and by immunohistochemical analysis in synovial tissue. The expression and function of the potential VIP receptors in FLS were studied by RT-PCR, determination of intracellular cAMP production, cell membrane adenylate cyclase (AC) activity, and interleukin-6, CCL2, and CXCL8 production in response to VIP or specific agonists and antagonists.Results. VIP expression was detected in human FLS at the messenger RNA and protein levels, and it was significantly decreased in RA FLS compared with OA FLS. VIP receptor type 1 (VPAC 1 ) was the dominant AC-coupled receptor in OA FLS, in contrast with RA FLS, in which VPAC 2 was dominant. Tumor necrosis factor ␣-treated OA FLS reproduced the VIP and VPAC receptor expression pattern of RA FLS. The antagonistic effects of VIP on FLS proinflammatory factor production were reproduced by VPAC 1 -and VPAC 2 -specific agonists in OA FLS and RA FLS, respectively.Conclusion. VIP expression is down-regulated in RA and in tumor necrosis factor ␣-treated FLS, suggesting that down-regulation of this endogenous antiinflammatory factor may contribute to the pathogenesis of RA. In RA FLS, VPAC 2 mediates the antiinflammatory effects of VIP, suggesting that VPAC 2 agonists may be an alternative to VIP as antiinflammatory agents.The vasoactive intestinal peptide (VIP)/pituitary adenylate cyclase-activating peptide (PACAP) system consists of 2 peptides and 3 receptors: VIP receptor type 1 (VPAC 1 ), VPAC 2 , and PACAP type 1 (PAC 1 ) receptor. These receptors belong to family 2 of the G proteincoupled receptors, which in recent years have shown remarkable antiinflammatory and immunomodulatory properties (1-3). VPAC 1 is constitutively expressed in macrophages and lymphocytes and binds VIP and PACAP with equal affinity (1,3). VPAC 2 has also been described in lymphocytes and macrophages as an inducible receptor after T cell receptor triggering or lipopolysaccharide (LPS) stimulation (1,3). The bestcharacterized effects of VIP/PACAP on immune cells are mediated by the adenylate cyclase (AC) pathway coupled to these receptors. Finally, the PAC 1 receptor is the PACAP-specific receptor, although at high concentrations VIP is a heterologous ligand (4). Endogenous VIP and PACAP can be produced by both neural and immune cells, but their regulation and participation in the pathogenesis of human inflammation are not known.

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Section: Discussionmentioning

confidence: 89%

Differential expression of vasoactive intestinal peptide and its functional receptors in human osteoarthritic and rheumatoid synovial fibroblasts

Juarranz

Gutiérrez‐Cañas

Santiago

et al. 2008

Arthritis & Rheumatism

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“…Human hematopoietic stem cells that are enriched for CD34 + cells derived from either bone marrow or cord blood (CB) have been shown to predominately express VPAC1 verses VPAC2 as assessed by semi-quantitative PCR, subtractive hybridization and western analysis [54,55] . Also, the immature, non-dividing CD34 +…”

Section: Vpac Receptor Expression Profile In Hematopoiesismentioning

confidence: 99%

“…The signaling induced by VPAC1 due to added VIP ligand (10 -9 mol/L) to these hematopoietic stem precursor cells showed a synergic effect on myeloid and mixed colony growth of CD34 + CB cells with little to no detectable effect on BM cells in the presence, but not absence of three early cytokines, FLT3 ligand, stem cell factor (STF) and thrombopoietin (TPO) [55] . Another study confirmed high levels of VPAC1 mRNA in BM cells, but exogenously added VIP (10 -13 to 10 -7 mol/L) instead suppressed erythroid and myeloid colony growth, with a concomitant increase in transforming growth factor (TGF)-β and tumor necrosis factor (TNF)-α from an unidentified stromal cell type (possibly macrophages) [54] .…”

Section: Cd38mentioning

confidence: 99%

Vasoactive intestinal peptide signaling axis in human leukemia

Dorsam

Benton²,

Failing³

et al. 2011

WJBC

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The vasoactive intestinal peptide (VIP) signaling axis constitutes a master "communication coordinator" between cells of the nervous and immune systems. To date, VIP and its two main receptors expressed in T lymphocytes, vasoactive intestinal peptide receptor (VPAC)1 and VPAC2, mediate critical cellular functions regulating adaptive immunity, including arresting CD4 T cells in G1 of the cell cycle, protection from apoptosis and a potent chemotactic recruiter of T cells to the mucosa associated lymphoid compartment of the gastrointestinal tissues. Since the discovery of VIP in 1970, followed by the cloning of VPAC1 and VPAC2 in the early 1990s, this signaling axis has been associated with common human cancers, including leukemia. This review highlights the present day knowledge of the VIP ligand and its receptor expression profile in T cell leukemia and cell lines. Also, there will be a discussion describing how the anti-leukemic DNA binding transcription factor, Ikaros, regulates VIP receptor expression in primary human CD4 T lymphocytes and T cell lymphoblastic cell lines (e.g. Hut-78). Lastly, future goals will be mentioned that are expected to uncover the role of how the VIP signaling axis contributes to human leukemogenesis, and to establish whether the VIP receptor signature expressed by leukemic blasts can provide therapeutic and/or diagnostic information.

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“…(4,16,32) in which HCMV also reactivates with greater frequency (26,33,40,43,51,80). VIP receptors are expressed on progenitors of neuronal, hepatic, retinal pigment epithelial, and hematopoietic cells (6,7,35,82). On the basis of this information, VIP was further studied in the HCMV reactivation model.…”

Section: Cells and Virusesmentioning

confidence: 99%

Breaking Human Cytomegalovirus Major Immediate-Early Gene Silence by Vasoactive Intestinal Peptide Stimulation of the Protein Kinase A-CREB-TORC2 Signaling Cascade in Human Pluripotent Embryonal NTera2 Cells

Yuan

Liu

et al. 2009

J Virol

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. We speculate that neurohormonal stimulation via this signaling cascade is a possible means for reversing HCMV silence in vivo.Persons with impaired cellular immunity risk tissue-invasive disease from reactivation of latent human cytomegalovirus (HCMV). HCMV reactivation in tissues or blood of immunocompetent patients suffering illness from another cause also occurs but usually goes unnoticed and is self-limiting. For instance, nearly one-third of patients who are critically ill or in septic shock have detectable findings of HCMV reactivation in their bloodstream (12,26,43,45,80). HCMV reactivation infection in intestinal tissues with preexisting inflammatory disease (e.g., inflammatory bowel disease) is also well described for immunocompetent patients (28,39,40,51). The precise triggering mechanisms that underlie HCMV reactivation are unknown.So far, only cells of myeloid lineage have been determined to fulfill criteria for cellular sites of HCMV latency in vivo. In healthy HCMV-seropositive persons, precursors of macrophages and dendritic cells, including CD34ϩ hematopoietic progenitor cells, carry latent HCMV genomes at a low frequency (75). The terminal differentiation of these cells into a macrophage-or dendritic cell-like phenotype is a prerequisite for HCMV reactivation ex vivo (67, 76). However, this reactivation appears to be a rare event, suggesting that other, as yet unidentified factors may promote HCMV reactivation. Stimulation with tumor necrosis factor alpha (TNF-␣) or gamma interferon may promote HCMV reactivation from differentiated counterparts of monocytic-dendritic cell precursors that had been infected latently in vitro or in vivo (25,66,67,76).For both HCMV and murine CMV, viral major immediateearly (MIE) gene expression is greatly restricted or shut off during viral latency, and the productive viral life cycle cannot advance without this expression (57,74,75,78). The MIE enhancer/promoter controlling expression is regulated by the coordinated actions of multiple types of cis-acting elements (57). These elements are bound by cellular transcription factors whose functions are modulated by input supplied by the cell, the virus, and the external surrounding (57). Higher-order chromatin structure contributes to this regulation. Heterochromatin components amass on the inactive MIE enhancer/promoter in viral latency, whereas the chromatin signatures of transcriptional activity predominate at the active MIE enhancer/ promoter in acute and reactivation infections (47,67). MIE enhancer/promoter silencing is also favored by innate antiviral mechanisms that partly involve the repressive actions of nuclear ND10 domain components (e.g., hDAXX, PML, ATRX, and histone deacetylase [HDAC]) (52) but does not involve CpG methylation of the MIE enhancer/promoter (29).Quiescent HCMV infection of human NTera2/D1 cells (NT2 cells) is a tractable model system for studying the regulation of HCMV MIE enhancer/promoter reactivation (37, 54). NT2 cells share many phenotypic features with pluripotent

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Preferential expression of the vasoactive intestinal peptide (VIP) receptor VPAC1 in human cord blood-derived CD34+CD38− cells: possible role of VIP as a growth-promoting factor for hematopoietic stem/progenitor cells

Cited by 17 publications

References 48 publications

Differential expression of vasoactive intestinal peptide and its functional receptors in human osteoarthritic and rheumatoid synovial fibroblasts

Differential expression of vasoactive intestinal peptide and its functional receptors in human osteoarthritic and rheumatoid synovial fibroblasts

Vasoactive intestinal peptide signaling axis in human leukemia

Breaking Human Cytomegalovirus Major Immediate-Early Gene Silence by Vasoactive Intestinal Peptide Stimulation of the Protein Kinase A-CREB-TORC2 Signaling Cascade in Human Pluripotent Embryonal NTera2 Cells

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