Involvement of IL‑10 and granulocyte colony‑stimulating factor in the fate of monocytes controlled by galectin‑1

  • Authors:
    • Da‑En Cheng
    • Wei‑An Chang
    • Jen‑Yu Hung
    • Ming‑Shyan Huang
    • Po‑Lin Kuo
  • View Affiliations

  • Published online on: September 16, 2014     https://doi.org/10.3892/mmr.2014.2573
  • Pages: 2389-2394
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Abstract

The process of differentiation from monocytes to dendritic cells is critical in immune modulation. Monocyte apoptosis is a key regulator in balancing the immune response. Galectin‑1 has been reported to induce tolerogenic dendritic cells by the autocrine interleukin (IL)‑10 in monocytes. However, IL‑10 has been found to induce apoptosis in IL‑4/granulocyte macrophage colony‑stimulating factor (CSF) stimulating and non‑stimulating monocytes, whereas galectin‑1 has not. After analyzing the factors secreted by galectin-1-activated CD14 monocytes isolated from the peripheral blood, the present study revealed that galectin‑1 upregulates IL‑10 and granulocyte (G)-CSF expression. Furthermore, G‑CSF inhibited IL‑10‑induced apoptosis, implying that galectin‑1 may enhance the immune‑modulating functions of G‑CSF by inducing tolerogenic dendritic cells and maintaining their survival. Therefore, G‑CSF may be further applied in immune therapy, particularly in the IL‑10‑presenting microenvironment.

Introduction

Dendritic cells (DCs) are specific antigen-presenting cells critical for the induction of adaptive immunity and tolerance by interacting with T cells (1). DC differentiation from monocytes is a key step in infections and numerous other conditions. DC turnover is similarly important for maintaining the steady state of the immune system. Circulating monocytes usually undergo spontaneous apoptosis within days (2); however, the life span of monocytes is extended to weeks following differentiation into DCs, induced by treatment with interleukin (IL)-4/granulocyte macrophage colony-stimulating factor (GM-CSF).

Previous studies have observed that T-helper (Th)1 cytokines, including IL-2 and IL-12, inhibit myeloid cell apoptosis, whereas Th2 cytokines, such as IL-4 and IL-10, enhance apoptosis in these cells (3,4). IL-10-induced myeloid cell apoptosis is mediated through the caspase-dependent signaling pathway, which is blocked by caspase-3 inhibitors and pan-caspase inhibitors (2). Galectin-1 (Gal-1) exhibits the ability to induce IL-10 expression in T cells (5,6) and in DCs (7,8), but does not induce apoptosis in monocytes (9,10).

Granulocyte colony-stimulating factor (G-CSF, also termed CSF3) was identified in an attempt to define the normal regulators present in cell supernatants that induced terminal differentiation of the WEHI-3B D+ murine myeloid leukemia cell line (11). Recently, Romero-Weaver et al reported the ability of G-CSF to promote the proliferation of bone marrow stem cells and inhibit granulocyte apoptosis (12). G-CSF also improved the recovery from spinal cord injury in mice (13) and improved memory and neuro-behavior in an amyloid-β-induced experimental model of Alzheimer’s disease (14). However, the direct effects of G-CSF on differentiating monocytes have not been discussed. In present study, the role of G-CSF in galectin-1-treated monocytes was examined, particularly its role in preventing cell apoptosis.

Materials and methods

Materials

Gal-1 and G-CSF were purchased from ProsPec-Tany TechnoGene, Ltd. (Ness-Ziona, Israel). Human recombinant IL-10 was purchased from R&D Systems (Minneapolis, MN, USA). Human recombinant GM-CSF and IL-4 were purchased from Millipore Corp. (Billerica, MA, USA).

Isolation and culture of human monocytes

Human CD14+ monocytes were isolated from the peripheral blood mononuclear cells (PBMCs) of healthy donors without any known cancers or immunological disease. Briefly, PBMCs were collected from interphase subsequent to Ficoll paque plus separation (GE Healthcare Bio-Sciences, Little Chalfont, UK) and washed twice in phosphate-buffered saline (PBS). CD14+ monocytes were isolated using the MACS® system (MACS MicroBeads; Miltenyi Biotec Ltd, Bergisch Gladbach, Germany) following the manufacturer’s instructions and cultured in RPMI-1640 containing 10% fetal bovine serum (Invitrogen Life Sciences, Carlsbad, CA, USA) for five days in the presence of 20 ng/ml IL-4/GM-CSF with or without 1 μg/ml Gal-1, 10 ng/ml G-CSF and IL-10 as indicated. Monocyte viability was determined by trypan blue exclusion staining.

The Institutional Review Board of Kaohsiung Medical University Hospital (Kaohsiung, Taiwan) approved the study. All patients provided informed consent in accordance with the Declaration of Helsinki.

Flow cytometry and detection of Annexin V staining and CD14 expression

Two-color flow cytometry was performed by FACSarray (BD Biosciences, Franklin Lakes, NJ, USA) using the Annexin V-fluorescein isothiocyanate (FITC) Apoptosis Detection kit I (BD Biosciences) according to the manufacturer’s instructions. Briefly, the treated cells were centrifuged at 200 × g for 5 min and washed twice with cold PBS. The cells were resuspended in 100 μl 1× binding buffer, and 5 μl Annexin V-FITC and 5 μl propidium iodide (PI) were added. The cells were gently vortexed and incubated for 15 min at room temperature in the dark. Subsequently, the cells were centrifuged at 200 × g for 5 min, washed twice with 1× binding buffer and resuspended in 100 μl 1× binding buffer. The samples were analyzed using a FACSarray flow cytometer.

Measurement of secreted factors

The cultured supernatants from monocytes were collected following centrifugation. The samples were analyzed for IL-10 and G-CSF by multiple cytokine analyses using the cytometric bead array (CBA; BD Biosciences). The CBA technique is based on two bead populations with distinct fluorescence intensities that are coated with capture antibodies specific for each cytokine. The fluorescent dye had a maximal emission wavelength of ~650 nm (FL-3), which was detectable by flow cytometry. The cytokine capture beads were mixed with the phycoerythrin-conjugated detection antibodies and then incubated with recombinant standards or test samples to form sandwich complexes. Following the acquisition of sample data on the FACSarray flow cytometer, the sample results were analyzed using FCAP Array™ software version 3.0 (BD Biosciences). A standard calibration curve was established for each cytokine; the maximum and minimum limits of detection for each cytokine were 1.0 and 5,000 pg/ml, respectively.

Statistical analysis

Data are expressed as the mean ± standard deviation. Statistical comparisons of the results were performed by analysis of variance and two-sided Student’s t-test using Excel 2010 (Microsoft Corp., Redmond, WA, USA). P<0.05 was considered to indicate a statistically significant difference between the means of the two groups.

Results

IL-10 induces apoptosis in monocytes

Monocytes isolated from PBMCs of healthy donors usually died after several days due to a constitutively active cell death program (15). This spontaneous cell death was reduced by 20% following stimulation with IL-4 and GM-CSF for five days (Fig. 1A). The viability of the stimulated monocytes, determined by trypan blue exclusion assay, was reduced when IL-10 was added and the proportion of trypan blue- stained cells increased following treatment with higher IL-10 concentrations (Fig. 1A). Similarly, Annexin V-PI staining revealed that the proportion of apoptotic cells was elevated with increasing IL-10 concentration and increased culture duration (Fig. 1B and C). The apoptosis induced by recombinant human IL-10 was significantly increased at concentrations >2.5 ng/ml.

Gal-1 protects monocytes from IL-10-induced apoptosis

The percentage of apoptotic cells was determined by Annexin V-propidium iodide staining of the IL-4/GM-CSF-stimulating monocyte culture media with and without 1 μg/ml Gal-1 and/or 10 ng/ml IL-10. Stimulated monocyte apoptosis in the IL-10-only group continuously increased over five days. The Gal-1-only group exhibited no increase in apoptosis after three days (Fig. 2A). Furthermore, IL-10+Gal-1-stimulated monocyte apoptosis was not increased after three days (Fig. 2A). The same phenomenon was observed in monocytes isolated from five donors, although the percentage of apoptotic cells varied (Fig. 2B).

Gal-1 induces IL-10 and G-CSF in stimulated monocytes

The supernatants of the Gal-1 only group were collected after five days of incubation and analyzed by the CBA system. The concentrations of >10 cytokines (i.e. IL-1, -4, -6, -8, -10, -11, -12, -17 and -21, interferons (IFNs), the tumor necrosis factors (TNFs), basic fibroblast growth factor, vascular endothelial growth factor and G-CSF) were determined, with GM-CSF serving as an internal control. Gal-1 enhanced the expression levels of IL-6, IL-10 and G-CSF, but not those of the other cytokines (Fig. 3A–C).

G-CSF inhibits IL-10-induced apoptosis in monocytes

When IL-10 (10 ng/ml) was added to the IL-4/GM-CSF-stimulated monocyte culture media with and without Gal-1 (1 μg/ml) and G-CSF (10 ng/ml), analysis of stimulated monocyte apoptosis revealed that recombinant human G-CSF or Gal-1 significantly inhibited IL-10-induced apoptosis (P<0.05 as compared with IL-10-only treated cells; Fig. 4A and B).

Discussion

The fate of monocytes is regulated by different signaling pathways, including those of NF-κB, Fas-Fas ligand (FasL) and the B-cell lymphoma 2 (Bcl-2) family. A previous study reported that spontaneous monocyte apoptosis was inhibited by treatment with inflammatory mediators, including TNF, lipopolysaccharide (LPS), CD40 ligand (CD154), growth factors and cytokines, including GM-CSF and IFN-γ (16). Alone, IL-4 does not inhibit spontaneous apoptosis, and may inhibit the anti-apoptotic effects of IL-1 and LPS (3,17). However, co-treatment with GM-CSF and IL-4, according to the monocyte-derived DC protocol, inhibits the spontaneous apoptosis of monocytes (17). This implies that the signaling pathway involved in the anti-apoptotic effect mediated by GM-CSF may be different from the signaling pathway induced by IL-1 and LPS.

Receptors of pro-inflammatory mediators, including TNF receptor, IL-1R, Toll-like receptor 4 and CD14, activate the NF-κB signaling pathway and upregulate anti-apoptotic genes (18). Conversely, the GM-CSF receptor activates the Janus kinase (JAK)/signal transducer and activator of transcription (STAT)5 signaling pathway and upregulates Bcl-2 in neural progenitor cells and mouse hematopoietic precursors (19,20).

Studies regarding IL-4 and IL-6 in monocytes support the hypothesis that IL-4 inhibits IL-6 production by reducing nuclear NF-κB levels (21,22). However, the interaction between the IL-4 signaling pathway and STAT5 in monocytes has not been reported. Notably, in the present study, apoptosis enhanced by another Th2 cytokine, IL-10, was not inhibited by the presence of GM-CSF, suggesting a difference between IL-10-induced apoptosis and apoptosis enhanced by IL-4. Hashimoto et al (23) obtained similar results and further demonstrated that IL-10 inhibited the phosphorylation of STAT5 induced by GM-CSF. In another study, Schmidt et al (24) found that CD95 ligand-neutralizing antibody significantly inhibited IL-10-induced apoptosis. In conclusion, IL-10 may induce apoptosis by inhibiting STAT5 and by activating the Fas/FasL signaling pathway.

Galectins are a family of 15 β-galactoside-binding proteins. Gal-1 is a 14.5 kDa protein and was the first galectin family member to be described. Dimeric Gal-1 binds to glycoproteins and activates signaling pathways, including those of CD4, CD7, CD43 and CD45 (2528). Numerous studies have demonstrated that Gal-1 induces apoptosis in T cells (25,2832) and macrophages (33), which may be involved in the regulation of immune responses. The signaling pathway involved in Gal-1-mediated T-cell death requires clarification, as data remain inconclusive due to variations in Gal-1 interacting proteins and concentrations (34).

A study revealed that Gal-1 regulates the T-cell immune response through upregulating IL-10 expression; Gal-1 did not induce apoptosis in myeloid lineage and Th cells, but did increase the regulatory T-cell population (35). In another model, recombinant Gal-1 enhanced IL-10 expression levels up to seven-fold, but the apoptosis induced by high dosages of IL-10 was not observed, implying that other signaling pathways activated by Gal-1 inhibit the pro-apoptotic effects of IL-10 (36). In the present study, Gal-1 enhanced IL-6 and G-CSF expression levels up to twelve- and nine-fold, respectively, but not the expression levels of pro-inflammatory cytokines (i.e. TNF, IFN and IL-12; data not shown). Mangan and Wahl (37) reported that IL-6 exerted no effect on non-stimulating apoptosis; this was also observed in later studies (5,6). The present study demonstrated that IL-6 did not inhibit IL-10-induced apoptosis in IL-4/GM-CSF-stimulated monocytes. However, another hematopoietic growth factor induced by Gal-1, G-CSF, was found to reduce IL-10-induced apoptosis.

G-CSF is the predominant regulator of neutrophil production under basal conditions of hematopoiesis. G-CSF maintains neutrophil survival (38,39) and regulates the survival and mobilization of cardiomyocytes and neurons (4042). The G-CSF receptor belongs to the cytokine receptor type I superfamily, which engages the canonical JAK/STAT, Ras/Raf/mitogen-activated protein kinase and protein kinase B signaling pathways, all of which are crucial for the anti-apoptotic function of G-CSF (43,44).

The present study demonstrated that G-CSF not only exerted an anti-apoptotic effect on monocytes, but also inhibited IL-10-induced apoptosis without affecting the tolerogenic function of IL-10 (data not shown). Examining the network of cytokines that regulate the fate of monocytes, this implies that Gal-1 reinforces its immune modulating effects by simultaneously upregulating IL-10 and G-CSF. Therefore, G-CSF may be further applied in immune therapy, particularly in the IL-10-presenting microenvironment.

Acknowledgements

This study was supported by grants from the National Science Council of Taiwan (no. NSC 101-2628-B-037-001-MY3) and the Kaohsiung Medical University Hospital (no. KMUH102-2M09). The authors would like to thank the Centre for Resources, Research and Development of Kaohsiung Medical University for support with the instrumentation.

References

1 

Janikashvili N, Bonnotte B, Katsanis E and Larmonier N: The dendritic cell-regulatory T lymphocyte crosstalk contributes to tumor-induced tolerance. Clin Dev Immunol. 2011:4303942011. View Article : Google Scholar : PubMed/NCBI

2 

Fahy RJ, Doseff AI and Wewers MD: Spontaneous human monocyte apoptosis utilizes a caspase-3-dependent pathway that is blocked by endotoxin and is independent of caspase-1. J Immunol. 163:1755–1762. 1999.

3 

Estaquier J and Ameisen JC: A role for T-helper type-1 and type-2 cytokines in the regulation of human monocyte apoptosis. Blood. 90:1618–1625. 1997.PubMed/NCBI

4 

Ludewig B, Graf D, Gelderblom HR, Becker Y, Kroczek RA and Pauli G: Spontaneous apoptosis of dendritic cells is efficiently inhibited by TRAP (CD40-ligand) and TNF-alpha, but strongly enhanced by interleukin-10. Eur J Immunol. 25:1943–1950. 1995. View Article : Google Scholar : PubMed/NCBI

5 

van der Leij J, van den Berg A, Harms G, et al: Strongly enhanced IL-10 production using stable galectin-1 homodimers. Mol Immunol. 44:506–513. 2007.

6 

van der Leij J, van den Berg A, Blokzijl T, et al: Dimeric galectin-1 induces IL-10 production in T-lymphocytes: an important tool in the regulation of the immune response. J Pathol. 204:511–518. 2004.PubMed/NCBI

7 

Kuo PL, Hung JY, Huang SK, et al: Lung cancer-derived galectin-1 mediates dendritic cell anergy through inhibitor of DNA binding 3/IL-10 signaling pathway. J Immunol. 186:1521–1530. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Ilarregui JM, Croci DO, Bianco GA, et al: Tolerogenic signals delivered by dendritic cells to T cells through a galectin-1-driven immunoregulatory circuit involving interleukin 27 and interleukin 10. Nat Immunol. 10:981–991. 2009. View Article : Google Scholar : PubMed/NCBI

9 

Stowell SR, Qian Y, Karmakar S, et al: Differential roles of galectin-1 and galectin-3 in regulating leukocyte viability and cytokine secretion. J Immunol. 180:3091–3102. 2008. View Article : Google Scholar : PubMed/NCBI

10 

Barrionuevo P, Beigier-Bompadre M, Ilarregui JM, et al: A novel function for galectin-1 at the crossroad of innate and adaptive immunity: galectin-1 regulates monocyte/macrophage physiology through a nonapoptotic ERK-dependent pathway. J Immunol. 178:436–445. 2007. View Article : Google Scholar

11 

Welte K, Platzer E, Lu L, et al: Purification and biochemical characterization of human pluripotent hematopoietic colony-stimulating factor. Proc Natl Acad Sci USA. 82:1526–1530. 1985. View Article : Google Scholar : PubMed/NCBI

12 

Romero-Weaver AL, Wan XS, Diffenderfer ES, Lin L and Kennedy AR: Kinetics of neutrophils in mice exposed to radiation and/or granulocyte colony-stimulating factor treatment. Radiat Res. 180:177–188. 2013. View Article : Google Scholar

13 

Guo Y, Zhang H, Yang J, et al: Granulocyte colony-stimulating factor improves alternative activation of microglia under microenvironment of spinal cord injury. Neuroscience. 15:2382013.PubMed/NCBI

14 

Prakash A, Medhi B and Chopra K: Granulocyte colony stimulating factor (GCSF) improves memory and neurobehavior in an amyloid-β induced experimental model of Alzheimer’s disease. Pharmacol Biochem Behav. 110:46–57. 2013.PubMed/NCBI

15 

Doseff AI: Apoptosis: the sculptor of development. Stem Cells Dev. 13:473–483. 2004. View Article : Google Scholar : PubMed/NCBI

16 

Kiener PA, Davis PM, Starling GC, et al: Differential induction of apoptosis by Fas-Fas ligand interactions in human monocytes and macrophages. J Exp Med. 185:1511–1516. 1997. View Article : Google Scholar : PubMed/NCBI

17 

Mangan DF, Robertson B and Wahl SM: IL-4 enhances programmed cell death (apoptosis) in stimulated human monocytes. J Immunol. 148:1812–1816. 1992.PubMed/NCBI

18 

Gaur U and Aggarwal BB: Regulation of proliferation, survival and apoptosis by members of the TNF superfamily. Biochem Pharmacol. 66:1403–1408. 2003. View Article : Google Scholar : PubMed/NCBI

19 

Choi JK, Kim KH, Park H, Park SR and Choi BH: Granulocyte macrophage-colony stimulating factor shows anti-apoptotic activity in neural progenitor cells via JAK/STAT5-Bcl-2 pathway. Apoptosis. 16:127–134. 2011. View Article : Google Scholar : PubMed/NCBI

20 

Feldman GM, Rosenthal LA, Liu X, et al: STAT5A-deficient mice demonstrate a defect in granulocyte-macrophage colony-stimulating factor-induced proliferation and gene expression. Blood. 90:1768–1776. 1997.

21 

Donnelly RP, Crofford LJ, Freeman SL, et al: Tissue-specific regulation of IL-6 production by IL-4. Differential effects of IL-4 on nuclear factor-kappa B activity in monocytes and fibroblasts. J Immunol. 151:5603–5612. 1993.PubMed/NCBI

22 

Takeshita S, Gage JR, Kishimoto T, Vredevoe DL and Martínez-Maza O: Differential regulation of IL-6 gene transcription and expression by IL-4 and IL-10 in human monocytic cell lines. J Immunol. 156:2591–2598. 1996.PubMed/NCBI

23 

Hashimoto SI, Komuro I, Yamada M and Akagawa KS: IL-10 inhibits granulocyte-macrophage colony-stimulating factor-dependent human monocyte survival at the early stage of the culture and inhibits the generation of macrophages. J Immunol. 167:3619–3625. 2001. View Article : Google Scholar

24 

Schmidt M, Lügering N, Pauels HG, Schulze-Osthoff K, Domschke W and Kucharzik T: IL-10 induces apoptosis in human monocytes involving the CD95 receptor/ligand pathway. Eur J Immunol. 30:1769–1777. 2000. View Article : Google Scholar : PubMed/NCBI

25 

Nguyen JT, Evans DP, Galvan M, et al: CD45 modulates galectin-1-induced T cell death: regulation by expression of core 2 O-glycans. J Immunol. 167:5697–5707. 2001. View Article : Google Scholar : PubMed/NCBI

26 

Pang M, He J, Johnson P and Baum LG: CD45-mediated fodrin cleavage during galectin-1 T cell death promotes phagocytic clearance of dying cells. J Immunol. 182:7001–7008. 2009. View Article : Google Scholar : PubMed/NCBI

27 

Fulcher JA, Chang MH, Wang S, et al: Galectin-1 co-clusters CD43/CD45 on dendritic cells and induces cell activation and migration through Syk and protein kinase C signaling. J Biol Chem. 284:26860–26870. 2009. View Article : Google Scholar : PubMed/NCBI

28 

Perillo NL, Pace KE, Seilhamer JJ and Baum LG: Apoptosis of T cells mediated by galectin-1. Nature. 378:736–739. 1995. View Article : Google Scholar : PubMed/NCBI

29 

Stillman BN, Hsu DK, Pang M, et al: Galectin-3 and galectin-1 bind distinct cell surface glycoprotein receptors to induce T cell death. J Immunol. 176:778–789. 2006. View Article : Google Scholar : PubMed/NCBI

30 

Garín MI, Chu CC, Golshayan D, Cernuda-Morollón E, Wait R and Lechler RI: Galectin-1: a key effector of regulation mediated by CD4+ CD25+ T cells. Blood. 109:2058–2065. 2007.PubMed/NCBI

31 

Pace KE, Hahn HP, Pang M, Nguyen JT and Baum LG: CD7 delivers a pro-apoptotic signal during galectin-1-induced T cell death. J Immunol. 165:2331–2334. 2000. View Article : Google Scholar : PubMed/NCBI

32 

Perillo NL, Uittenbogaart CH, Nguyen JT and Baum LG: Galectin-1, an endogenous lectin produced by thymic epithelial cells, induces apoptosis of human thymocytes. J Exp Med. 185:1851–1858. 1997. View Article : Google Scholar : PubMed/NCBI

33 

Paclik D, Werner L, Guckelberger O, Wiedenmann B and Sturm A: Galectins distinctively regulate central monocyte and macrophage function. Cell Immunol. 271:97–103. 2011. View Article : Google Scholar : PubMed/NCBI

34 

Cedeno-Laurent F and Dimitroff CJ: Galectin-1 research in T cell immunity: past, present and future. Clin Immunol. 142:107–116. 2012. View Article : Google Scholar : PubMed/NCBI

35 

van der Leij J, van den Berg A, Harms G, et al: Strongly enhanced IL-10 production using stable galectin-1 homodimers. Mol Immunol. 44:506–513. 2007.PubMed/NCBI

36 

Stowell SR, Qian Y, Karmakar S, et al: Differential roles of galectin-1 and galectin-3 in regulating leukocyte viability and cytokine secretion. J Immunol. 180:3091–3102. 2008. View Article : Google Scholar : PubMed/NCBI

37 

Mangan DF and Wahl SM: Differential regulation of human monocyte programmed cell death (apoptosis) by chemotactic factors and pro-inflammatory cytokines. J Immunol. 147:3408–3412. 1991.PubMed/NCBI

38 

Liu F, Wu HY, Wesselschmidt R, Kornaga T and Link DC: Impaired production and increased apoptosis of neutrophils in granulocyte colony-stimulating factor receptor-deficient mice. Immunity. 5:491–501. 1996. View Article : Google Scholar : PubMed/NCBI

39 

Lieschke GJ, Grail D, Hodgson G, et al: Mice lacking granulocyte colony-stimulating factor have chronic neutropenia, granulocyte and macrophage progenitor cell deficiency, and impaired neutrophil mobilization. Blood. 84:1737–1746. 1994.

40 

Shim W, Mehta A, Lim SY, et al: G-CSF for stem cell therapy in acute myocardial infarction: friend or foe? Cardiovasc Res. 89:20–30. 2011. View Article : Google Scholar : PubMed/NCBI

41 

Schneider A, Krüger C, Steigleder T, et al: The hematopoietic factor G-CSF is a neuronal ligand that counteracts programmed cell death and drives neurogenesis. J Clin Invest. 115:2083–2098. 2005. View Article : Google Scholar : PubMed/NCBI

42 

Schneider A, Kuhn HG and Schäbitz WR: A role for G-CSF (granulocyte-colony stimulating factor) in the central nervous system. Cell Cycle. 4:1753–1757. 2005. View Article : Google Scholar : PubMed/NCBI

43 

Harada M, Qin Y, Takano H, et al: G-CSF prevents cardiac remodeling after myocardial infarction by activating the Jak-Stat pathway in cardiomyocytes. Nat Med. 11:305–311. 2005. View Article : Google Scholar : PubMed/NCBI

44 

Fukada T, Hibi M, Yamanaka Y, et al: Two signals are necessary for cell proliferation induced by a cytokine receptor gp130: involvement of STAT3 in anti-apoptosis. Immunity. 5:449–460. 1996. View Article : Google Scholar : PubMed/NCBI

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Cheng DE, Chang WA, Hung JY, Huang MS and Kuo PL: Involvement of IL‑10 and granulocyte colony‑stimulating factor in the fate of monocytes controlled by galectin‑1. Mol Med Rep 10: 2389-2394, 2014
APA
Cheng, D., Chang, W., Hung, J., Huang, M., & Kuo, P. (2014). Involvement of IL‑10 and granulocyte colony‑stimulating factor in the fate of monocytes controlled by galectin‑1. Molecular Medicine Reports, 10, 2389-2394. https://doi.org/10.3892/mmr.2014.2573
MLA
Cheng, D., Chang, W., Hung, J., Huang, M., Kuo, P."Involvement of IL‑10 and granulocyte colony‑stimulating factor in the fate of monocytes controlled by galectin‑1". Molecular Medicine Reports 10.5 (2014): 2389-2394.
Chicago
Cheng, D., Chang, W., Hung, J., Huang, M., Kuo, P."Involvement of IL‑10 and granulocyte colony‑stimulating factor in the fate of monocytes controlled by galectin‑1". Molecular Medicine Reports 10, no. 5 (2014): 2389-2394. https://doi.org/10.3892/mmr.2014.2573