A Specific Stimulator of Granulocyte Colony-Stimulating Factor Accelerates Recovery From Cyclophosphamide-Induced Neutropenia in the Mouse

Fine, Jay S.; Cai, Xiao-Yan; Justice, Luminita; Gommoll, Carl; Hamilton, Linda D.; Waters, Tracey A.; Narula, Satwant K.; Bober, Loretta A.; Grace, Michael J.

doi:10.1182/blood.v90.2.795.795_795_802

Cited by 2 publications

(3 citation statements)

References 24 publications

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“…Because of this, efforts have been made to identify small molecular weight compounds that can be delivered at low cost as an effective therapy. A small synthetic compound, SCH 14988 (a pyridinyl-naphthyridinyl-sulfonyl acetamide), has been shown to specifically stimulate G-CSF production in vitro and in vivo [ 21 ]. In addition, Aoki et al [ 22 ] identified a stimulatory monoclonal antibody (mAb 3-4H7) from autoimmune mice that selectively stimulates G-CSF gene expression in mouse macrophages.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, Aoki et al [ 22 ] identified a stimulatory monoclonal antibody (mAb 3-4H7) from autoimmune mice that selectively stimulates G-CSF gene expression in mouse macrophages. The mechanism(s) by which SCH 14988 and mAb 3-4H7 stimulate G-CSF production is unclear, but post-transcriptional regulation has been suggested in the case of SCH 14988-stimulated G-CSF production [ 21 ]. Our study demonstrated that a small molecular weight compound, SB203580, can increase the G-CSF mRNA levels through a post-transcriptional mechanism by increasing the stability of mRNA.…”

Section: Discussionmentioning

confidence: 99%

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SB203580 increases G-CSF production via a stem-loop destabilizing element in the 3’ untranslated region in macrophages independently of its effect on p38 MAPK activity

Chang

Huang

et al. 2016

J Biomed Sci

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BackgroundGranulocyte-colony stimulating factor (G-CSF) is a major regulator of the production and survival of neutrophils. Regulation of G-CSF expression is complex and occurs at both transcription and post-transcription levels. Two distinct types of cis-acting elements in the 3’ untranslated region (3’UTR) of G-CSF mRNA have been identified as destabilizing elements; these consist of adenylate uridylate-rich elements (AUREs) and a stem–loop destabilizing element (SLDE). Regulation of the stability of mRNA by p38 mitogen-activated protein kinase (MAPK) has been indicated to be linked to AUREs in the 3’UTR. However, whether p38 MAPK is involved in the regulation of the stability of G-CSF mRNA has not been elucidated. This study investigated the effect of SB203580, an inhibitor of p38 MAPK, on the lipopolysaccharide-induced G-CSF expression in macrophages at the post-transcription level.ResultsOur study showed surprising results that SB203580 augmented the lipopolysaccharide-induced increase in the G-CSF mRNA levels in RAW264.7 mouse macrophages, mouse bone marrow-derived macrophages and in THP-1 human macrophages. This effect was also seen in p38α MAPK knockdown RAW264.7 cells, showing that it was not due to inhibition of p38 MAPK activity. In the presence of actinomycin D, the decay of G-CSF mRNA was slower in SB203580-treated cells than in control cells, showing that SB203580 increased the stability of G-CSF mRNA. Reporter genes containing luciferase with or without the 3’UTR of G-CSF were constructed and transfected into RAW264.7 cells and the results showed that the presence of the 3’UTR reduced the luciferase mRNA levels and luciferase activity. Furthermore, SB203580 increased the luciferase mRNA levels and activity in RAW264.7 cells transfected with the luciferase reporter containing the 3’UTR, but not in cells transfected with the luciferase reporter without the 3’UTR. Mutations of the highly conserved SLDE in the 3’UTR abolished these effects, showing that the SLDE was essential for the SB203580-induced increase in the stability of mRNA.ConclusionsSB203580 increases G-CSF expression in macrophages by increasing the stability of G-CSF mRNA via its 3’UTR, and the effect was not due to its inhibition of p38 MAPK activity. The results of this study also highlight a potential target for boosting endogenous production of G-CSF during neutropenia.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

SB203580 increases G-CSF production via a stem-loop destabilizing element in the 3’ untranslated region in macrophages independently of its effect on p38 MAPK activity

Chang

Huang

et al. 2016

J Biomed Sci

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“…In recent years, several protective agents have been used to reduce the toxic side effects of chemotherapy. These include administration of certain herbal remedies [Matsumoto et al, 1995;Kaneko et al, 1999;Latha and Panikkar, 1999] and chemoprotective agents [Moore and Warren, 1987;Futami et al, 1990;Chudgar et al, 1995;Fine et al, 1997;Misaki et al, 1998], which induce hematopoiesis resulting in accelerated recovery from myelosuppression and leukopenia caused by cancer chemotherapy. It is believed that these protective agents stimulate production of cytokines involved in proliferation, differentiation, and maturation of bone marrow cells.…”

Section: Introductionmentioning

confidence: 99%

Combined millimeter wave and cyclophosphamide therapy of an experimental murine melanoma

Logani

Bhanushali

Anga

et al. 2004

Bioelectromagnetics

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The objective of the present studies was to investigate whether millimeter wave (MMW) therapy can increase the efficacy of cyclophosphamide (CPA), a commonly used anti-cancer drug. The effect of combined MMW-CPA treatment on melanoma growth was compared to CPA treatment alone in a murine model. MMWs were produced with a Russian made YAV-1 generator. The device produced 42.2 +/- 0.2 GHz modulated wave radiation through a 10 x 20 mm rectangular output horn. The animals, SKH-1 hairless female mice, were irradiated on the nasal area. Peak SAR and incident power density were measured as 730 +/- 100 W/kg and 36.5 +/- 5 mW/cm2, respectively. The maximum skin surface temperature elevation measured at the end of 30 min irradiation was 1.5 degrees C. B16F10 melanoma cells (0.2 x 10(6)) were implanted subcutaneously into the left flank of mice on day 1 of the experiment. On days 4-8, CPA was administered intraperitoneally (30 mg/kg/day). MMW irradiation was applied concurrently with, prior to or following CPA administration. A significant reduction (P < .05) in tumor growth was observed with CPA treatment, but MMW irradiation did not provide additional therapeutic benefit as compared to CPA alone. Similar results were obtained when MMW irradiation was applied both prior to and following CPA treatment.

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A Specific Stimulator of Granulocyte Colony-Stimulating Factor Accelerates Recovery From Cyclophosphamide-Induced Neutropenia in the Mouse

Cited by 2 publications

References 24 publications

SB203580 increases G-CSF production via a stem-loop destabilizing element in the 3’ untranslated region in macrophages independently of its effect on p38 MAPK activity

SB203580 increases G-CSF production via a stem-loop destabilizing element in the 3’ untranslated region in macrophages independently of its effect on p38 MAPK activity

Combined millimeter wave and cyclophosphamide therapy of an experimental murine melanoma

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