The granulocyte colony stimulating factor (G‐CSF) activates Jak/STAT and MAPK pathways in a trophoblastic cell line

Marino, Julieta; Roguin, Leonor P.

doi:10.1002/jcb.21542

Cited by 58 publications

(58 citation statements)

References 49 publications

(97 reference statements)

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“…G-CSF has multiple effects on the immune system like induction of the Th2 answer (Pan et al 1995) and inhibition of NK cells (Schlahsa et al 2011) and blood mononuclear cells (Kitabayashi et al 1995;Sugita et al 2003). Moreover, experiments on animals and cell lines have proven a protective impact on fetuses (Novales et al 1993) and trophoblast cells (Marino and Roguin 2008).…”

Section: Discussionmentioning

confidence: 99%

Granulocyte-Colony Stimulating Factor as Treatment Option in Patients with Recurrent Miscarriage

Santjohanser¹,

Knieper

Franz

et al. 2013

Arch. Immunol. Ther. Exp.

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In 1-5 % of patients during childbearing years recurrent miscarriages (RM) occur. There are established risk factors like anatomical, endocrine and hemostatic disorders as well as immunological changes in the maternal immune system. Nevertheless, further elucidation of the pathogenesis remains a matter of debate. In addition, there are no standardized immunological treatment strategies. Recent studies indicate possible effects of tumor necrosis factor a blocker and granulocyte-colony stimulating factor (G-CSF) concerning live birth rate (LBR) in RM patients. Therefore, we performed a retrospective cohort study in patients undergoing assisted reproductive treatment (ART) with known RM analysing the possible benefits of G-CSF application. From January 2002 to December 2010, 127 patients (199 cylces) with RM (at least 2 early miscarriages) 49 (72 cycles) receiving G-CSF and 78 (127 cycles) controls receiving either no medication (subgroup 1) or Cortisone, intravenous immunoglobulins or low molecular weight heparin (subgroup 2) undergoing ART for in vitro fertilisation/intracytoplasmic sperm injection were analysed. G-CSF was administered weekly once (34 Mill) in 11 patients, 38 patients received 2 9 13 Mill G-CSF per week until the 12th week of gestation. Statistical analysis was performed with SPSS for Windows (19.0), p \ 0.05 significant. The mean age of the study population was 37.3 ± 4.4 years (mean ± standard deviation) and differed not significantly between patients and subgroups. However, the number of early miscarriages was significantly higher in the G-CSF group as compared to the subgroups (G-CSF 2.67 ± 1.27, subgroup 1 0.85 ± 0.91, subgroup 2 0.64 ± 0.74) and RM patients receiving G-CSF had significantly more often a late embryo transfer (day 5) (G-CSF 36.7 %, subgroup 1 12.1 %, subgroup 2 8.9 %). The LBR of patients and the subgroups differed significantly (G-CSF 32 %, subgroup 1 13 %, subgroup 2 14 %). Side effects were present in less than 10 % of patients, consisting of irritation at the injection side, slight leukocytosis, rise of the temperature (\38°C), mild bone pain and hyperemesis gravidarum. None of the newborn showed any kind of malformations. According to our data, G-CSF seems to be a safe and promising immunological treatment option for RM patients. However, with regard to the retrospective setting and the possible bias of a higher rate of late embryo transfers in the G-CSF group additional studies are needed to further strengthen our results.

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Section: Discussionmentioning

confidence: 99%

Granulocyte-Colony Stimulating Factor as Treatment Option in Patients with Recurrent Miscarriage

Santjohanser¹,

Knieper

Franz

et al. 2013

Arch. Immunol. Ther. Exp.

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“…It has, for example, also been described that both, the G-CSF receptor (growth hormone receptor family) and the GM-CSF receptor (gp-140 receptor family) on the surface of myeloid progenitors, mature neutrophils, monocytes and endothelial cells can act via the same steps of the JAK/STAT pathway [32,33]. …”

Section: Discussionmentioning

confidence: 99%

Granulocyte Colony-Stimulating Factor Improves Cerebrovascular Reserve Capacity by Enhancing Collateral Growth in the Circle of Willis

Duelsner¹,

Gatzke²,

Gläser³

et al. 2012

Cerebrovasc Dis

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Background and Purpose: Restoration of cerebrovascular reserve capacity (CVRC) depends on the recruitment and positive outward remodeling of preexistent collaterals (arteriogenesis). With this study, we provide functional evidence that granulocyte colony-stimulating factor (G-CSF) augments therapeutic arteriogenesis in two animal models of cerebral hypoperfusion. We identified an effective dosing regimen that improved CVRC and stimulated collateral growth, thereby improving the outcome after experimentally induced stroke. Methods: We used two established animal models of (a) cerebral hypoperfusion (mouse, common carotid artery ligation) and (b) cerebral arteriogenesis (rat, 3-vessel occlusion). Following therapeutic dose determination, both models received either G-CSF, 40 µg/kg every other day, or vehicle for 1 week. Collateral vessel diameters were measured following latex angiography. Cerebrovascular reserve capacities were assessed after acetazolamide stimulation. Mice with left common carotid artery occlusion (CCAO) were additionally subjected to middle cerebral artery occlusion, and stroke volumes were assessed after triphenyltetrazolium chloride staining. Given the vital role of monocytes in arteriogenesis, we assessed (a) the influence of G-CSF on monocyte migration in vitro and (b) monocyte counts in the adventitial tissues of the growing collaterals in vivo. Results: CVRC was impaired in both animal models 1 week after induction of hypoperfusion. While G-CSF, 40 µg/kg every other day, significantly augmented cerebral arteriogenesis in the rat model, 50 or 150 µg/kg every day did not show any noticeable therapeutic impact. G-CSF restored CVRC in mice (5 ± 2 to 12 ± 6%) and rats (3 ± 4 to 19 ± 12%). Vessel diameters changed accordingly: in rats, the diameters of posterior cerebral arteries (ipsilateral: 209 ± 7–271 ± 57 µm; contralateral: 208 ± 11–252 ± 28 µm) and in mice the diameter of anterior cerebral arteries (185 ± 15–222 ± 12 µm) significantly increased in the G-CSF groups compared to controls. Stroke volume in mice (10 ± 2%) was diminished following CCAO (7 ± 4%) and G-CSF treatment (4 ± 2%). G-CSF significantly increased monocyte migration in vitro and perivascular monocyte numbers in vivo. Conclusion: G-CSF augments cerebral collateral artery growth, increases CVRC and protects from experimentally induced ischemic stroke. When comparing three different dosing regimens, a relatively low dosage of G-CSF was most effective, indicating that the common side effects of this cytokine might be significantly reduced or possibly even avoided in this indication.

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“…STAT3 is activated in a sustained fashion, but activation of STAT5 is transient, with maximal activation levels occurring within 10 to 30 minutes. [7][8][9][10] STAT5 is involved in the maintenance and expansion of human hematopoietic stem/progenitor cells and is crucial for cell survival and proliferation. 11 In myeloid progenitors lacking both STAT5a and STAT5b, the clonal advantage conferred by mutant G-CSFR was found to be abrogated.…”

Section: Introductionmentioning

confidence: 99%

Bortezomib inhibits STAT5-dependent degradation of LEF-1, inducing granulocytic differentiation in congenital neutropenia CD34+ cells

Gupta¹,

Kuznetsova²,

Klimenkova³

et al. 2014

Blood

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The granulocyte colony stimulating factor (G‐CSF) activates Jak/STAT and MAPK pathways in a trophoblastic cell line

Cited by 58 publications

References 49 publications

Granulocyte-Colony Stimulating Factor as Treatment Option in Patients with Recurrent Miscarriage

Granulocyte-Colony Stimulating Factor as Treatment Option in Patients with Recurrent Miscarriage

Granulocyte Colony-Stimulating Factor Improves Cerebrovascular Reserve Capacity by Enhancing Collateral Growth in the Circle of Willis

Bortezomib inhibits STAT5-dependent degradation of LEF-1, inducing granulocytic differentiation in congenital neutropenia CD34+ cells

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