Cloning of Human Preprotachykinin-I Promoter and the Role of Cyclic Adenosine 5′-Monophosphate Response Elements in Its Expression by IL-1 and Stem Cell Factor

Qian, Jing; Yehia, Ghassan; Molina, Carlos A.; Fernandes, A.; Donnelly, Robert; Anjaria, Devashish J.; Gascón, Pedro; Rameshwar, Pranela

doi:10.4049/jimmunol.166.4.2553

Cited by 48 publications

(84 citation statements)

References 38 publications

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“…Total RNA (15 g) was analyzed with a specific cDNA probe for ␤-PPT-I, as previously described (17). The probe was randomly labeled with [␣-32 P]dATP, 3,000 Ci/mM, (DuPont Pharmaceuticals), as described (18). Membranes were stripped and reprobed with cDNA for 18S rRNA.…”

Section: Northern Analysismentioning

confidence: 99%

“…pGL3-Basic vectors containing inserts of the 5Ј flanking regions of Tac1 (PPT-I/1.2 and PPT-I/N0) were previously described (18). Briefly, the gene-specific insert of PPT-I/1.2 is equivalent to 1.2 kb and includes intron 1, exon 1, and upstream sequences.…”

Section: Vectorsmentioning

confidence: 99%

“…EMSA for NF-B binding was performed as described (18). Doublestranded oligonucleotides were synthesized at the Molecular Core Facility of the New Jersey Medical School (Newark, NJ).…”

Section: Emsamentioning

confidence: 99%

“…The consensus sequence for NF-B is underlined (18). Mutant sequences changed the third G to A (G3 A and the eighth T to G (T3 G).…”

Section: Emsamentioning

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: Northern Analysismentioning

confidence: 99%

Section: Vectorsmentioning

confidence: 99%

“…EMSA for NF-B binding was performed as described (18). Doublestranded oligonucleotides were synthesized at the Molecular Core Facility of the New Jersey Medical School (Newark, NJ).…”

Section: Emsamentioning

confidence: 99%

“…The consensus sequence for NF-B is underlined (18). Mutant sequences changed the third G to A (G3 A and the eighth T to G (T3 G).…”

Section: Emsamentioning

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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“…PPT-I peptides may be involved in tumor cell invasiveness and metastasis. 74 Peptide receptors such as PPT-I receptors are under investigation as molecular targets for cancer treatment. 75 In the bone marrow, there are two major PPT-I receptors: Neurokinin-1 and -2 (NK-1R and NK-2R).…”

Section: Neuropeptides and Bone Metastasismentioning

confidence: 99%

Biology of breast cancer bone metastasis

Akhtari

Mansuri²,

Newman³

et al. 2008

Cancer Biology & Therapy

139

110

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Breast carcinoma ranks among the most prevalent malignancies in women. Breast carcinoma frequently metastasizes to bone and approximately 70% of patients with breast cancer have bone metastases, which generally are osteolytic lesions. They cause major morbidity and mortality in patients; and the available treatment options are limited. Bone-specific homing and colonization of cancer cells are important and interesting features of metastasis. There are complex and multiple steps in the process of bone metastasis; and the elaborate interaction between breast carcinoma and bone involves various cytokines, growth factors and cellular signals, which results in a vicious cycle and promotes tumor cell accumulation and osteolysis. Recent advances in molecular biology have resulted in major breakthroughs in our understanding of the pathogenesis of bone metastasis in breast cancer, which is critical in preventing metastasis, designing novel and targeted treatments and prolonging survival in this devastating condition.

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A non‐peptide substance P antagonist (CP‐96,345) inhibits morphine‐induced NF‐κB promoter activation in human NT2‐N neurons

Wang¹,

Douglas²,

Commons³

et al. 2003

J of Neuroscience Research

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Opioids and the neuropeptide substance P (SP) modulate the expression of inflammatory cytokines and chemokines, which are under the control of nuclear factor kappaB (NF-kappaB). We investigated whether the neurokinin-1 receptor (SP receptor) pathway is biologically involved in morphine-mediated modulation of NF-kappaB promoter activation in a human neuronal cell line (NT2-N) that expresses both the mu-opioid receptor (MOR) and the SP receptor. Morphine significantly enhanced NF-kappaB promoter-directed luciferase activity in NT2-N neurons. DAMGO, a selective mu-opioid receptor agonist, also induced NF-kappaB promoter activation. The induced activation of NF-kappaB promoter by morphine or DAMGO was abolished not only by naltrexone (a opioid receptor antagonist) and CTAP (a selective, competitive mu-opioid receptor antagonist), but also by CP-96,345, a non-peptide SP receptor antagonist. Investigation of the mechanism responsible for morphine-induced activation of NF-kappaB promoter in NT2-N neurons demonstrated that morphine activates the SP promoter and induces SP expression in these cells. We also observed that SP activated NF-kappaB promoter and that CP-96,345 downregulated the expression of endogenous SP. Furthermore, dual immunofluorescent labeling revealed that there is co-expression of NK-1R and MOR in the processes of NT-2N neurons. These results suggest that morphine, by activating MOR, engages a positive feedback loop between NK-1R and SP. Activation of NK-1R could then impact NF-kappaB expression and therefore may be an important participant in the effect of morphine on immune responses in the central nervous system.

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Cloning of Human Preprotachykinin-I Promoter and the Role of Cyclic Adenosine 5′-Monophosphate Response Elements in Its Expression by IL-1 and Stem Cell Factor

Cited by 48 publications

References 38 publications

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

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

Biology of breast cancer bone metastasis

A non‐peptide substance P antagonist (CP‐96,345) inhibits morphine‐induced NF‐κB promoter activation in human NT2‐N neurons

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