Crosstalk between neurokinin receptors is relevant to hematopoietic regulation: cloning and characterization of neurokinin-2 promoter

Bandari, Persis; Qian, Jing; Oh, Hyun Sook; Potian, Julius A.; Yehia, Ghassan; Harrison, Jonathan S.; Rameshwar, Pranela

doi:10.1016/s0165-5728(03)00096-1

Cited by 29 publications

(49 citation statements)

References 35 publications

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“…These are intriguing observations that should be explored further in future studies. Also, the lack of evidence for autocrine stimulation of stroma by SP to produce SDF-1␣ further supports receptor crosstalk between NK1 and NK2 (5). Despite the evidence of intracellular crosstalk between NK1 and NK2, the molecular mechanism of this occurrence is unknown.…”

Section: Discussionmentioning

confidence: 98%

“…Tac1 produces several peptides that belong to the tachykinin family with substance P (SP) and neurokinin-A as its major gene products (4). SP and neurokinin-A interact with different binding affinities to three related seven-transmembrane G protein-coupled receptors: neurokinin (NK) 1, NK2, and NK3 (5,6).…”

mentioning

confidence: 99%

“…NK1 and NK2 mediate stimulatory and inhibitory effects on hemopoiesis, respectively (5). NK2 is constitutively expressed in unstimulated BM stroma, whereas NK1 expression requires induction by cytokines with stimulatory effects on hemopoiesis and by broad-acting cytokines such as IL-1 (7).…”

mentioning

confidence: 99%

“…NK2 is constitutively expressed in unstimulated BM stroma, whereas NK1 expression requires induction by cytokines with stimulatory effects on hemopoiesis and by broad-acting cytokines such as IL-1 (7). The expression of NK1 correlates with down-regulation of NK2 on normal hemopoietic cells and BM stroma (5). Although the mechanism involved in this yin-yang type of expression between NK1 and NK2 is unclear, the experimental evidence suggests mechanisms involving intracellular crosstalk (5).…”

mentioning

confidence: 99%

“…The expression of NK1 correlates with down-regulation of NK2 on normal hemopoietic cells and BM stroma (5). Although the mechanism involved in this yin-yang type of expression between NK1 and NK2 is unclear, the experimental evidence suggests mechanisms involving intracellular crosstalk (5). The regulated expressions of NK1 and NK2 in the BM stroma affect hemopoiesis, mainly because one receptor subtype appears to modulate the functions of the other (1,4).…”

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confidence: 99%

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Stromal Derived Growth Factor-1α: Another Mediator in Neural-Emerging Immune System through Tac1 Expression in Bone Marrow Stromal Cells

Corcoran¹,

Patel²,

Rameshwar

2007

The Journal of Immunology

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Stromal cell-derived growth factor-1α (SDF-1α) is a member of the CXC chemokines and interacts with the G protein, seven-transmembrane CXCR4 receptor. SDF-1α acts as a chemoattractant for immune and hemopoietic cells. The Tac1 gene encodes peptides belonging to the tachykinin family with substance P being the predominant member. Both SDF-1α and Tac1 peptides are relevant hemopoietic regulators. This study investigated the effects of SDF-1α on Tac1 expression in the major hemopoietic supporting cells, the bone marrow stroma, and addresses the consequence to hemopoiesis. Reporter gene assays with the 5′ flanking region of Tac1 showed a bell-shaped effect of SDF-1α on luciferase activity with 20 ng/ml SDF-1α acting as stimulator, whereas 50 and 100 ng/ml SDF-1α acted as inhibitors. Gel shift assays and transfection with wild-type and mutant IκB indicate NF-κB as a mediator in the repressive effects at 50 and 100 ng/ml SDF-1α. Northern analyses and ELISA showed correlations among reporter gene activities, mRNA (β-preprotachykinin I), and protein levels for substance P. Of relevance is the novel finding by long-term culture-initiating cell assays that showed an indirect effect of SDF-1α on hemopoiesis through substance P production. The results also showed neurokinin 1 and not neurokinin 2 as the relevant receptor. Another crucial finding is that substance P does not regulate the production of SDF-1α in stroma. The studies indicate that SDF-1α levels above baseline production in bone marrow stroma induce the production of substance P to stimulate hemopoiesis. Substance P, however, does not act as autocrine stimulator to induce the production of SDF-1α. This study adds SDF-1α as a mediator within the neural-immune-hemopoietic axis.

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Section: Discussionmentioning

confidence: 98%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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