Recent developments and potentialities for reducing embryo mortality in ruminants: the role of IFN-t and other cytokines in early pregnancy

1997 ◽  
Vol 9 (3) ◽  
pp. 355 ◽  
Author(s):  
J. Martal ◽  
Nicole ChÊne ◽  
Sylvaine Camous ◽  
L. Huynh ◽  
F. Lantier ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Interleukin 2 ◽  
Prostaglandin F2α ◽  
Fetal Mortality ◽  
Uterine Receptivity ◽  
Embryo Survival ◽  
Embryo Mortality ◽  
Ifn Γ

This review considers the potential reduction of embryo mortality in vitro and in vivo in ruminants. Data on cytokines provided by different fields of reproductive immunology and biology were collated. Because of the crucial importance of the local interactions between the embryo and its dam, the expression of growth-factor and cytokine genes was analysed in the embryo proper, trophoblast, oviduct and endometrium by reverse transcriptase polymerase chain reaction in sheep and in cattle during the pre- and periimplantation periods. Many deleterious cytokines, such as tumour necrosis factor-α, intereron-γ (IFN-γ ), interleukin-2 (IL-2), and beneficial cytokines, such as transforming growth factor-β, leukaemia inhibiting factor, colony-stimulating factor-1 (CSF-1), ganulocyte–macrophage CSF, IL-1, IL-3, IL-4, IL-6, IL-10 and IFN-γ appeared to be involved in embryo survival in ruminants and other species. Their administration is efficient in a murine experimental model (CBA/J DBA/2) of embryonic and fetal mortality. For instance, recombinant ovine IFN-τ (roIFN-τ ) injected at the moment of implantation drastically reduces embryonic mortality in this model. In ruminants, roIFN-τ and recombinant bovine IFN-τ are very efficient in maintaining progesterone luteal secretion in cyclic animals. The involvement of IFN-τ in the mechanisms of maternal pregnancy recognition are particularly detailed in relation to inbition of 13,14 dihydro-15-keto-prostaglandin F2α (PGFM) pulses and oxytocin uterine receptivity. A synthetic model of the anti-luteolytic effects of IFN-τ on the endometrial cell is proposed. Finally, the particular potential of serum pregnancy-specific proteins (PSPs: PSPB, PSP60, pregnancy-associated glycoprotein) for monitoring embryo survival, with examples given for cattle and sheep is underlined.

scholarly journals Effects of Gamma Interferon, Interleukin-10, and Transforming Growth Factor β on the Survival of Mycobacterium avium subsp. paratuberculosis in Monocyte-Derived Macrophages from Naturally Infected Cattle

2004 ◽  
Vol 72 (4) ◽  
pp. 1974-1982 ◽  
Author(s):  
M. S. Khalifeh ◽  
J. R. Stabel
Keyword(s):  
Growth Factor ◽  
Cell Cultures ◽  
Mycobacterium Avium ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Interleukin 10 ◽  
Gamma Interferon ◽  
Ifn Γ ◽  
Culture Supernatants

ABSTRACT Gamma interferon (IFN-γ) plays a significant role in the control of mycobacterial infections, including Mycobacterium avium subsp. paratuberculosis. However, the contribution of other immunoregulatory cytokines, such as interleukin-10 (IL-10) and transforming growth factor β (TGF-β), in Johne's disease has not been investigated as yet. In this study, we examined the effects of in vivo and in vitro infection with M. avium subsp. paratuberculosis on the production of IFN-γ, IL-10, and TGF-β by peripheral blood mononuclear cells (PBMC). We also examined the effects of exogenous IFN-γ, IL-10, and TGF-β on M. avium subsp. paratuberculosis survival in the cell cultures. PBMC obtained from naturally infected cows, regardless of their disease status, specifically upregulated IL-10 and TGF-β in culture supernatants in response to stimulation with live M. avium subsp. paratuberculosis. Nonstimulated PBMC recovered from subclinically infected animals secreted the lowest levels of TGF-β, but after stimulation with live M. avium subsp. paratuberculosis, TGF-β levels in the culture supernatants increased to levels similar to that produced by PBMC from healthy animals. The numbers of viable M. avium subsp. paratuberculosis recovered from cultures from naturally infected animals were higher than those from healthy cows after in vitro infection with M. avium subsp. paratuberculosis. The addition of exogenous IL-10 and TGF-β to PBMC isolated from healthy cows inhibited the bactericidal activity of these cells as evidenced by the increased number of viable M. avium subsp. paratuberculosis recovered from these cultures compared to cell cultures containing medium alone. These data suggest important immune regulatory roles for IL-10 and TGF-β during infection with M. avium subsp. paratuberculosis that may be directly related to their effects on macrophage activation and killing of M. avium subsp. paratuberculosis.

scholarly journals Interleukin-4 and Transforming Growth Factor β Have Opposing Regulatory Effects on Gamma Interferon-Mediated Inhibition of Cryptosporidium parvum Reproduction

2003 ◽  
Vol 71 (8) ◽  
pp. 4580-4585 ◽  
Author(s):  
I.-Sarah Lean ◽  
Stuart A. C. McDonald ◽  
Mona Bajaj-Elliott ◽  
Richard C. G. Pollok ◽  
Michael J. G. Farthing ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cryptosporidium Parvum ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Inhibitory Effect ◽  
Gamma Interferon ◽  
Interleukin 4 ◽  
Effector Cells ◽  
Ifn Γ

ABSTRACT It was shown previously that enterocytes activated by gamma interferon (IFN-γ) are efficient effector cells in the killing of Cryptosporidium parvum. How this function is regulated is not clearly understood, but transforming growth factor β (TGF-β) and the Th2 regulatory cytokines may play a role. Using an in vitro cell culture system, we investigated how the key regulatory cytokines interleukin-4 (IL-4), IL-10, IL-13, and TGF-β might modulate the effect of IFN-γ in inducing resistance to infection in enterocyte cell lines. The results showed that TGF-β can abolish the inhibitory effect on C. parvum development and that neither IL-13 nor IL-10 influenced the action of IFN-γ. In contrast, IL-4 cooperated with low concentrations of IFN-γ (1 and 10 U/ml) to enhance parasite killing. One mechanism that appeared to be involved in the combined activity of IFN-γ and IL-4 was intracellular Fe2+ deprivation, but induction of nitric oxide production was not involved. In one cell line, the extents and durations of phosphorylation of STAT1, a transcription factor involved in IFN-γ signaling, were similar when cells were stimulated with IFN-γ alone and with IFN-γ and IL-4γ, suggesting that the cooperative effect of the cytokines was not related to STAT1 activation. The effects of the presence of TGF-β and IL-4 on IFN-γ function did not appear to involve any alteration in the level of expression of IFN-γ receptors.

scholarly journals Krüppel-like factor KLF10 regulates transforming growth factor receptor II expression and TGF-β signaling in CD8+ T lymphocytes

2015 ◽  
Vol 308 (5) ◽  
pp. C362-C371 ◽  
Author(s):  
Konstantinos A. Papadakis ◽  
James Krempski ◽  
Jesse Reiter ◽  
Phyllis Svingen ◽  
Yuning Xiong ◽  
...  
Keyword(s):  
T Cells ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Critical Role ◽  
Effector Memory ◽  
Antiviral Immune Response ◽  
Ifn Γ ◽  
Tgf Β1

KLF10 has recently elicited significant attention as a transcriptional regulator of transforming growth factor-β1 (TGF-β1) signaling in CD4+ T cells. In the current study, we demonstrate a novel role for KLF10 in the regulation of TGF-β receptor II (TGF-βRII) expression with functional relevance in antiviral immune response. Specifically, we show that KLF10-deficient mice have an increased number of effector/memory CD8+ T cells, display higher levels of the T helper type 1 cell-associated transcription factor T-bet, and produce more IFN-γ following in vitro stimulation. In addition, KLF10−/− CD8+ T cells show enhanced proliferation in vitro and homeostatic proliferation in vivo. Freshly isolated CD8+ T cells from the spleen of adult mice express lower levels of surface TGF-βRII (TβRII). Congruently, in vitro activation of KLF10-deficient CD8+ T cells upregulate TGF-βRII to a lesser extent compared with wild-type (WT) CD8+ T cells, which results in attenuated Smad2 phosphorylation following TGF-β1 stimulation compared with WT CD8+ T cells. Moreover, we demonstrate that KLF10 directly binds to the TGF-βRII promoter in T cells, leading to enhanced gene expression. In vivo viral infection with Daniel's strain Theiler's murine encephalomyelitis virus (TMEV) also led to lower expression of TGF-βRII among viral-specific KLF10−/− CD8+ T cells and a higher percentage of IFN-γ-producing CD8+ T cells in the spleen. Collectively, our data reveal a critical role for KLF10 in the transcriptional activation of TGF-βRII in CD8+ T cells. Thus, KLF10 regulation of TGF-βRII in this cell subset may likely play a critical role in viral and tumor immune responses for which the integrity of the TGF-β1/TGF-βRII signaling pathway is crucial.

Prostaglandin F2α–PTGFR signalling activation, growth factor expression and cell proliferation in bovine endometrial explants

2017 ◽  
Vol 29 (11) ◽  
pp. 2195 ◽  
Author(s):  
Shuangyi Zhang ◽  
Bo Liu ◽  
Long Gao ◽  
Wei Mao ◽  
Changqi Fu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Protein Expression ◽  
Transforming Growth Factor ◽  
Prostaglandin F2α ◽  
Transforming Growth Factor Β1 ◽  
Specific Protein ◽  
Tissue Growth ◽  
Nuclear Antigen

The endometrium of domestic animals undergoes regular periods of regeneration and degeneration and exhibits a remarkable capacity for self-repair during the oestrous cycle. The endometrial growth pattern is also observed during in the implantation period and early pregnancy, but the mechanism underlying endometrial growth in these processes remains unclear. A positive correlation between endometrial growth in these processes and prostaglandin (PG) F2α secretion has been reported, but the roles that PGF2α plays in endometrial growth is less studied. In the present study, cell proliferation and the responses of a series of growth factors essential for endometrial growth to PGF2α receptor (PTGFR) activation were investigated in bovine endometrial explants in vitro. Using real-time reverse transcription–polymerase chain reaction and western blotting, mRNA and protein expression of connective tissue growth factor, fibroblast growth factor2, interleukin8, matrix metalloproteinase2, transforming growth factor β1 and vascular endothelial growth factor A was increased (P < 0.05) and cell proliferation, including epithelial and fibroblast proliferation, was induced in response to increased levels of proliferating cell nuclear antigen, cytokeratin-18 and fibroblast-specific protein-1 (P < 0.05) following PTGFR activation by adding fluprostenol (10−9–10−5 M) into culture medium of bovine endometrial explants. However, caspase-3 protein expression was reduced following treatment of explants with fluprostenol (10−9–10−5 M, P < 0.05). These results may help define the possible roles the PGF2α–PTGFR signalling pathway plays in endometrial growth.

scholarly journals Prostaglandin F2α promotes angiogenesis and embryo–maternal interactions during implantation

Reproduction ◽  
2016 ◽  
Vol 151 (5) ◽  
pp. 539-552 ◽  
Author(s):  
Piotr Kaczynski ◽  
Mariusz P Kowalewski ◽  
Agnieszka Waclawik
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Reproductive Tract ◽  
Transforming Growth Factor ◽  
Prostaglandin F2α ◽  
Expression Of Genes ◽  
Interleukin 1Α ◽  
Extraembryonic Membranes ◽  
Endothelial Growth Factor

AbstractImplantation in humans and other mammals is a critical period during which high embryonic mortality rates occur. Prostaglandins (PGs) are key mediators regulating interactions between the reproductive tract and the conceptus (embryo with extraembryonic membranes). Although the significance of PGF2α as a regulator of corpus luteum regression is well established, the role of its high amounts in the uterine lumen in most mammals, regardless of placentation type, during the implantation period remains unresolved. We hypothesized that PGF2α acting as an embryonic signal mediator contributes to pregnancy establishment. Using a porcine model, we demonstrated that the conceptus and its signal (estradiol-17β) elevated endometrial expression of PGF2α receptor (PTGFR)invivoandin vitro. PTGFR protein was expressed mainly in luminal epithelial (LE) and glandular epithelial cells and blood vessels in the endometrium. PGF2α stimulated the MAPK1/3 pathway in endometrial LE cells that coincided with elevated gene expression and secretion of endometrial vascular endothelial growth factor A (VEGFA) protein. PGF2α–PTGFR and adenylyl cyclase signaling were involved in this process. PGF2α-induced VEGFA acting through its receptors stimulated proliferation of endometrial endothelial cells. Moreover, PGF2α elevated gene expression of biglycan, matrix metalloproteinase 9, transforming growth factor β3, and interleukin 1α in the endometrium. In summary, our study indicates that PGF2α participates in pregnancy establishment by promoting angiogenesis and expression of genes involved in tissue remodeling and conceptus–maternal interactions in porcine endometrium during early pregnancy.

scholarly journals Interaction of Mycobacterium tuberculosis-Induced Transforming Growth Factor β1 and Interleukin-10

1999 ◽  
Vol 67 (11) ◽  
pp. 5730-5735 ◽  
Author(s):  
Catherine Othieno ◽  
Christina S. Hirsch ◽  
Beverly D. Hamilton ◽  
Katalin Wilkinson ◽  
Jerrold J. Ellner ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Growth Factor ◽  
Mononuclear Cells ◽  
Transforming Growth Factor ◽  
Interleukin 10 ◽  
Transforming Growth Factor Β1 ◽  
Ifn Γ ◽  
Tgf Β1

ABSTRACT Mycobacterium tuberculosis is associated with the activation of cytokine circuits both at sites of active tuberculosis in vivo and in cultures of mononuclear cells stimulated by M. tuberculosis or its components in vitro. Interactive stimulatory and/or inhibitory pathways are established between cytokines, which may result in potentiation or attenuation of the effects of each molecule on T-cell responses. Here we examined the interaction of transforming growth factor β1 (TGF-β1) and interleukin-10 (IL-10) in purified protein derivative (PPD)-stimulated human mononuclear cell cultures in vitro. TGF-β1 induced monocyte IL-10 (but not tumor necrosis factor alpha) production (by 70-fold, P < 0.02) and mRNA expression in the absence but not in the presence of PPD. Both exogenous recombinant (r) IL-10 and rTGF-β1 independently suppressed the production of PPD-induced gamma interferon (IFN-γ) in mononuclear cells from PPD skin test-positive individuals. Synergistic suppression of IFN-γ in cultures containing both rTGF-β1 and rIL-10 was only seen when the responder cell population were peripheral blood mononuclear cells (PBMC) and not monocyte-depleted mononuclear cells and when PBMC were pretreated with rTGF-β1 but not with rIL-10. Suppression of PPD-induced IFN-γ in PBMC containing both rTGF-β1 (1 ng/ml) and rIL-10 (100 pg/ml) was 1.5-fold higher (P< 0.05) than cultures containing TGF-β1 alone and 5.7-fold higher (P < 0.004) than cultures containing IL-10 alone. Also, neutralization of endogenous TGF-β1 and IL-10 together enhanced PPD-induced IFN-γ in PBMC in a synergistic manner. Thus, TGF-β1 and IL-10 together potentiate the downmodulatory effect on M. tuberculosis-induced T-cell production of IFN-γ, and TGF-β1 alone enhances IL-10 production. At sites of active M. tuberculosis infection, these interactions may be conducive to the suppression of mononuclear cell functions.

85 EFFECT OF FOLLICULAR ASPIRATION JUST PRIOR TO OVULATION ON CORPUS LUTEUM CHARACTERISTICS, CIRCULATING PROGESTERONE CONCENTRATIONS AND UTERINE RECEPTIVITY IN SINGLE-OVULATING BEEF HEIFERS

2012 ◽  
Vol 24 (1) ◽  
pp. 155 ◽  
Author(s):  
L. O'Hara ◽  
S. Scully ◽  
V. Maillo-Sevilla ◽  
A. K. Kelly ◽  
P. Duffy ◽  
...  
Keyword(s):  
Corpus Luteum ◽  
Embryo Development ◽  
Prostaglandin F2α ◽  
Uterine Receptivity ◽  
Beef Heifers ◽  
Embryo Survival ◽  
Follicular Aspiration ◽  
Follicle Aspiration ◽  
And Function

Progesterone (P4) has a crucial impact on the transcriptome of the uterine endometrium and the preparation of the uterus to support implantation. The aim of this study was to investigate the effect of follicle aspiration just before ovulation on corpus luteum (CL) development, circulating P4 concentrations and the ability of the uterus to support embryo development and conceptus elongation. We tested the hypothesis that the unavoidable loss of follicular fluid and some granulosa cells during aspiration of the preovulatory follicle would compromise the development and function of the developing CL and that this would be associated with reduced P4 and a poorer uterine environment. Oestrous cycles of crossbred beef heifers were synchronized using an 8-day CIDR treatment with administration of a prostaglandin F2α analogue on the day before CIDR removal to ensure CL regression. Heifers were checked for signs of oestrus 4 times per day commencing 30 h after CIDR withdrawal and only those recorded in standing oestrus (Day 0, n = 20) were used. All heifers received a gonadotropin-releasing hormone agonist (0.01 mg buserelin) 48 h after CIDR removal to induce an LH surge. Half of the animals underwent follicle aspiration 20 h later, while the remainder underwent ovulation. Daily transrectal ultrasonography was carried out from Day 3 to 13 to record CL development. Daily blood samples were collected from Day 0 to 14 for circulating P4 concentrations. To test the ability of the uterus to support embryo development and conceptus elongation, Day 7 in vitro-produced blastocysts were transferred to the uteri of synchronised recipients (7 to 10 blastocysts per recipient). All recipients were slaughtered on Day 14 to assess embryo survival and conceptus size. CL diameter and CL area were significantly reduced in the follicle aspirated group compared with controls from Day 6 onwards (P ≤ 0.05). Similarly, at slaughter on Day 14, CL weight (4.17 ± 0.48 vs 7.05 ± 1.65 mm), diameter (19.89 ± 1.35 vs 24.64 ± 2.07 mm) and area (321.94 ± 45.01 vs 510.18 ± 69.41 mm2) were lower in aspirated heifers (P ≤ 0.05). Circulating P4 concentrations were lower at all time points from Day 3 to Day 14 but were only significantly lower from Day 12 onwards (P ≤ 0.05). Conceptus length (2.08 ± 0.29, n = 56 vs 4.55 ± 0.78 mm, n = 45) and area (2.52 ± 0.39 vs 5.61 ± 1.12 mm2) were lower (P ≤ 0.05) in heifers undergoing follicular aspiration compared with those undergoing ovulation. In conclusion, aspiration of the preovulatory dominant follicle just before expected ovulation was associated with a compromised CL in terms of size and P4 output and this, in turn, was associated with a reduced capacity of the uterus to support the initiation of conceptus elongation. Supported by Science Foundation Ireland (07/SRC/B1156).

scholarly journals Control of CD4 effector fate: transforming growth factor beta 1 and interleukin 2 synergize to prevent apoptosis and promote effector expansion.

1995 ◽  
Vol 182 (3) ◽  
pp. 699-709 ◽  
Author(s):  
X Zhang ◽  
L Giangreco ◽  
H E Broome ◽  
C M Dargan ◽  
S L Swain
Keyword(s):  
Cell Death ◽  
T Cell ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Interleukin 2 ◽  
Cell Immune Response ◽  
Tgf Beta ◽  
Effector Cells

The signals that determine the size and duration of the primary T cell immune response are not well defined. We studied CD4 T cells at an important checkpoint in their development: when they have become effectors and are ready to rapidly mediate effector functions, both via direct interaction with antigen (Ag)-presenting cells and via cytokine production. We determined the effects of specific Ag and the cytokines interleukin (IL) 2 and transforming growth factor (TGF) beta 1 on T helper cell type 2 (Th2) effector apoptosis versus expansion. Th2-polarized effector cells were generated in vitro from naive CD4 T of T cell receptor transgenic mice, and then restimulated with or without peptide Ag plus Ag-presenting cells and cytokines. In the absence of added cytokines, effector cells cultured without Ag died of apoptosis after 4-7 d. Paradoxically, Ag both induced proliferation and high levels of cytokine synthesis and accelerated effector cell death. IL-2 directly induced proliferation of effectors, supported and prolonged Ag-induced proliferation, and partially blocked apoptosis. TGF-beta did not effect proliferation or influence cytokine secretion, but it also partially blocked apoptosis. Together, IL-2 and TGF-beta synergized to almost completely block apoptosis, resulting in prolonged effector expansion and leading to the accumulation of a large pool of specific effectors. When Ag and both cytokines were present, the effector population increased 10(4)-10(5) fold over 20 d of culture. The synergy of IL-2 and TGF-beta suggests that they interfere with programmed cell death by distinct mechanisms. Since Th2 effectors are specialized to help B cells develop into antibody-secreting plasma cells, these results suggest that the availability of Ag and of the cytokines IL-2 and TGF-beta is a key factor influencing the fate of Th2 effector cells and thus the size and duration of the primary antibody response.

Inhibition of lymphocyte function by glioblastoma-derived transforming growth factor β2

1989 ◽  
Vol 71 (2) ◽  
pp. 211-217 ◽  
Author(s):  
Maria C. Kuppner ◽  
Marie-France Hamou ◽  
Yutaka Sawamura ◽  
Stefan Bodmer ◽  
Nicolas de Tribolet
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Malignant Gliomas ◽  
Interleukin 2 ◽  
Inhibitory Effect ◽  
Lymphocyte Function ◽  
Suppressor Factor ◽  
Necrosis Factor Alpha

✓ Human glioblastoma cells secrete an inhibitory factor termed “glioblastoma-derived T-cell suppressor factor” (G-TsF). A member of the transforming growth factor beta (TGFβ) family, G-TsF is identical to TGFβ2. The present study investigated the effect of G-TsF/TGFβ2 on the proliferative and cytotoxic properties of tumor-infiltrating lymphocytes (TIL's) isolated from malignant gliomas after expansion in vitro with interleukin-2 (IL-2). The results demonstrate that the IL-2 (5 to 20 U/ml)-dependent proliferative response of glioma-derived TIL's was inhibited 70% to 85% by G-TsF/TGFβ2 and that the inhibitory effect could be reduced by using increasing concentrations of IL-2 (100 to 200 U/ml). Tumor necrosis factor alpha (TNFα) enhanced the IL-2-dependent proliferation of TIL's cultured in low concentrations of IL-2 (10 U/ml); however, neither TNFα nor interferon gamma was able to reduce the inhibitory effect of TGFβ2 on TIL proliferation. In addition, TGFβ2 suppressed 60% to 100% the cytotoxic response of glioma-derived TIL's against several tumor targets, including autologous glioma cells, and the suppressive effect was shown to be reduced by increasing concentrations of IL-2.

scholarly journals Immunomodulatory and antiangiogenic mechanisms of polymolecular botanical drug extract C5OSEW5050ESA OS derived from Orthosiphon stamineus

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Fouad Saleih R. Al-Suede ◽  
◽  
Mohamed B. Khadeer Ahamed ◽  
Aman S. Abdul Majid ◽  
Sultan Ayesh Mohammed Saghir ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Interleukin 2 ◽  
Drug Formulation ◽  
Endothelial Cell Proliferation ◽  
Interferon Α ◽  
Orthosiphon Stamineus ◽  
Botanical Drug

NuvastaticTM is a polymolecular botanical drug formulation containing a proprietary extract of a selected cultivar of Orthosiphon stamineus (OS) code name, C5OSEW5050ESA OS. The anti-angiogenic activity of C5OSEW5050ESA OS was explored by evaluating its activity towards a variety of angiogenesis modulators in vitro and in vivo. Multiplex immunoassays reveals that C5OSEW5050ESA OS inhibits Vascular Endothelial Growth factor (VEGF), Epidermal Growth Factor (EGF), Fibroblast Growth Factor (FGF), Interleukin 2 ( IL-2) & Interleukin 7 (IL-7), Nerve Growth Factor β (NGF-β) , Transforming Growth Factor -α (TGF-α) and Tumor Necrosis Factor- β (TNF-β). C5OSEW5050ESA OS also caused significant upregulation of interferon α (IFN-α), interferon β (IFN-β), interferon γ (IFN-γ) and Granulocyte-macrophage colony-stimulating factor (GM-CSF). C5OSEW5050ESA OS was found to inhibit endothelial cell proliferation and migration (92.6%) and disrupts the tube assembly (98.26%) for new blood vessel formation. The compound also inhibits neovascularisation in isolated rat aortic ring tissues (IC50 18.2 ± 2 µg/mL) and in chick chorioallantoic membrane assays (CAM) by 82.7%. In vivo matrigel plug assay treated with C5OSEW5050ESA OS shows inhibition of neovascularisation by 91.4± 3%. In conclusion, the study reveals that C5OSEW5050ESA OS has strong anti-angiogenic and immunomodulatory properties which may have significant clinical benefits in cancer therapy.

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