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Cytokines Promote Angiogenesis

Viviana Anelli, Marina Mione
Cancer-associated fibroblasts (CAFs) are an activated sub-population of stromal fibroblast that have the ability to synthesize, deposit and remodel the extracellular matrix. They produce and secrete cytokines and growth factors that promote tumor growth, angiogenesis, inflammation and contribute to drug resistance (Micke and Ostman, 2005). CAFs are abundant constituents of many epithelial tumors. Less is known about CAFs in non-epithelial cancers, such as melanoma, but in vitro data suggest similar roles in tumor development and progression (Kim et al...
October 23, 2016: Pigment Cell & Melanoma Research
Juri Bergmann, Miryam Müller, Niklas Baumann, Manuel Reichert, Carola Heneweer, Julia Bolik, Karsten Lücke, Sabine Gruber, Antonella Carambia, Susanne Boretius, Ivo Leuschner, Thomas Becker, Björn Rabe, Johannes Herkel, F Thomas Wunderlich, Hans-Willi Mitrücker, Stefan Rose-John, Dirk Schmidt-Arras
: Hepatocellular carcinoma (HCC) is one of the most frequent tumors worldwide with rising incidence. The inflammatory cytokine interleukin 6 (IL-6) is a critical mediator of HCC development. It can signal through two distinct pathways, the IL-6 classic and the IL-6 trans-signaling pathway. While IL-6 classic signaling is important for innate and acquired immunity, IL-6 trans-signaling has been linked to accelerated liver regeneration and several chronic inflammatory pathologies. However, its implication in liver tumorigenesis has not been addressed yet...
October 22, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Rania R Abdelaziz, Wagdi F Elkashef, Eman Said
Silicosis is a crippling respiratory disorder characterized by massive lung inflammation and fibrosis. The current study provides evidence on the protective potential of tadalafil; a specific phosphodiesterase-5 (PDE-5) inhibitor against experimentally-induced pulmonary silicosis in rats. Silicosis was induced by intranasal instillation of crystalline silica (50mg/rat). Halofuginone hydrobromide; a standard collagen-1 synthesis inhibitor was selected as a reference anti-fibrotic. Daily oral administration of tadalafil (1mg/kg) for 8weeks significantly ameliorated silica-induced pulmonary damage...
October 18, 2016: International Immunopharmacology
Monica D Prakash, Sarah Miller, Sarron Randall-Demllo, Kulmira Nurgali
Cancer development is often associated with chronic inflammation. To date, research into inflammation-induced cancer has largely focused on chemokines, cytokines, and their downstream targets. These inflammatory mediators may promote tumor growth, invasion, metastasis, and facilitate angiogenesis. However, the exact mechanisms by which inflammation promotes neoplasia remain unclear. Inflammatory bowel disease (IBD) is characterized by recurrent, idiopathic intestinal inflammation, the complications of which are potentially fatal...
November 2016: Inflammatory Bowel Diseases
Meng Wang, Yuanman Yu, Kai Dai, Zhengyu Ma, Yang Liu, Jing Wang, Changsheng Liu
Immune responses are vital for bone regeneration and play an essential role in the fate of biomaterials after implantation. As a kind of plastic cell, macrophages are central regulators of the immune response during the infection and wound healing process including osteogenesis and angiogenesis. Magnesium-calcium phosphate cement (MCPC) has been reported as a promising candidate for bone repair with promoted osteogenesis both in vitro and in vivo. However, relatively little is known about the effects of MCPC on immune response and the following outcome...
October 18, 2016: Biomaterials Science
Z Touat-Hamici, H Weidmann, Y Blum, C Proust, H Durand, F Iannacci, V Codoni, P Gaignard, P Thérond, M Civelek, A S Karabina, A J Lusis, F Cambien, E Ninio
AIMS: Lipid phosphate phosphatase 3 (LPP3; PPAP2B) is a transmembrane protein dephosphorylating and thereby terminating signalling of lipid substrates including lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P). Human LPP3 possesses a cell adhesion motif that allows interaction with integrins. A polymorphism (rs17114036) in PPAP2B is associated with coronary artery disease, which prompted us to investigate the possible role of LPP3 in human endothelial dysfunction, a condition promoting atherosclerosis...
September 30, 2016: Cardiovascular Research
Hao Lu, Xiaoyue Wu, Zejing Wang, Li Li, Wen Chen, Mingcan Yang, Da Huo, Wen Zeng, Chuhong Zhu
BACKGROUND: Mesenchymal stem cell (MSC) transplantation is an effective treatment therapy for ischemic ulcers. However, in high-glucose microenvironment, the original inflammation-inhibiting function of MSCs leads to turns into secreting large amounts of inflammatory mediators, such as tumor necrosis factor alpha, for example, which decreases their capacity and becomes poor quality stem cells over inflammation cells for diabetic foot ulcers repair in the healing of diabetic foot ulcers...
October 2016: Journal of Surgical Research
Anca Virtej, Panagiota Papadakou, Hajime Sasaki, Athanasia Bletsa, Ellen Berggreen
BACKGROUND: In apical periodontitis, oral pathogens provoke an inflammatory response in the apical area that induces bone resorptive lesions. In inflammation, angio- and lymphangiogenesis take place. Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are key players in these processes and are expressed in immune cells and endothelial cells in the lesions. OBJECTIVE: We aimed at testing the role of VEGFR-2 and -3 in periapical lesion development and investigated their role in lymphangiogenesis in the draining lymph nodes...
2016: Journal of Oral Microbiology
Bu-Nam Jeon, Jae-Hyeon Yoon, Min-Kyeong Kim, Won-Il Choi, Dong-In Koh, Benjamin Hur, Kunhong Kim, Kyung-Sup Kim, Man-Wook Hur
Matrix metalloproteinases (MMPs) are zinc-containing endopeptidases that play roles in cell proliferation, migration, differentiation, angiogenesis, and apoptosis. The expression of MMP gene is tightly regulated and shows cell- and tissue-specific expression patterns. Despite their differential expression, MMP genes have AP-1 (activator protein-1) binding elements within their promoters. Interestingly, c-JUN phosphorylation by cytokine signaling decreased its interaction with NCoR, but increased its interaction with p300, resulting in activation of MMP gene transcription...
September 17, 2016: Biochimica et Biophysica Acta
Dongyao Yan, Hao-Wei Wang, Robert L Bowman, Johanna A Joyce
Tumor-associated macrophages play critical roles during tumor progression by promoting angiogenesis, cancer cell proliferation, invasion, and metastasis. Cysteine cathepsin proteases, produced by macrophages and cancer cells, modulate these processes, but it remains unclear how these typically lysosomal enzymes are regulated and secreted within the tumor microenvironment. Here, we identify a STAT3 and STAT6 synergy that potently upregulates cathepsin secretion by macrophages via engagement of an unfolded protein response (UPR) pathway...
September 13, 2016: Cell Reports
Jonathan Rodness, Anton Mihic, Yasuo Miyagi, Jun Wu, Richard D Weisel, Ren-Ke Li
BACKGROUND: Revascularization of the heart after myocardial infarction (MI) using growth factors delivered by hydrogel-based microspheres represents a promising therapeutic approach for cardiac regeneration. Microspheres have tuneable degradation properties and support the prolonged release of soluble factors. Cardiac patches provide mechanical restraint, preventing dilatation associated with ventricular remodelling. METHODS: We combined these approaches and produced a compacted calcium-alginate microsphere patch, restrained by a chitosan sheet, to deliver vascular endothelial growth factor (VEGF) to the heart after myocardial injury in rats...
November 2016: Acta Biomaterialia
M Yao, G Brummer, D Acevedo, N Cheng
The human body combats infection and promotes wound healing through the remarkable process of inflammation. Inflammation is characterized by the recruitment of stromal cell activity including recruitment of immune cells and induction of angiogenesis. These cellular processes are regulated by a class of soluble molecules called cytokines. Based on function, cell target, and structure, cytokines are subdivided into several classes including: interleukins, chemokines, and lymphokines. While cytokines regulate normal physiological processes, chronic deregulation of cytokine expression and activity contributes to cancer in many ways...
2016: Advances in Cancer Research
Xiaosong Chen, Liu Yan, Zhihui Guo, Zhaohong Chen, Ying Chen, Ming Li, Chushan Huang, Xiaoping Zhang, Liangwan Chen
Autologous fat grafting is an effective reconstructive surgery technique; however, its success is limited by inconsistent graft retention and an environment characterized by high oxidative stress and inflammation. Adipose-derived stem cells (ADSCs) increase the survival of fat grafts, although the underlying mechanisms remain unclear. Here, TLR4(-/-) and Nrf2(-/-) mice were used to explore the effects of oxidative stress and inflammation on the viability and function of ADSCs in vitro and in vivo. Enrichment of fat grafts with ADSCs inhibited inflammatory cytokine production, enhanced growth factor levels, increased fat graft survival, downregulated NADPH oxidase (NOX)1 and 4 expression, increased vascularization and reduced ROS production in a manner dependent on toll-like receptor (TLR)-4 and nuclear factor erythroid 2-related factor 2 (Nrf2) expression...
2016: Cell Death & Disease
Iwona Homa-Mlak, Aleksandra Majdan, Radosław Mlak, Teresa Małecka-Massalska
In response to various stimuli, neutrophils and eosinophils can release neutrophil extracellular traps (NET) consisting of proteolytic enzymes, DNA and other components of the cell nucleus. The NETosis process has been characterized as a mechanism of programmed cell death, which leads to chromatin decondensation and disintegration of organelles, followed by lysis of the cell membrane. In recent years the significant role of neutrophils in the pathogenesis of cancer has been highlighted. The presence of two subpopulations of TAN with different phenotypes and functions - acting antitumor "N1" and the pro-cancerous "N2" - has been discovered...
2016: Postȩpy Higieny i Medycyny Doświadczalnej
Muneo Numasaki, Hiroki Tsukamoto, Yoshihisa Tomioka, Yasuhiko Nishioka, Takashi Ohrui
The interleukin (IL)-17 family, consisting of six homodimeric cytokines IL-17A, IL-17B, IL-17C, IL-17D, IL-17E/IL-25, and IL-17F, mediates a variety of biological activities including regulation of chemokine secretion and angiogenesis. Among the IL-17 family members, IL-17A and IL-17E/IL-25 are angiogenesis stimulators, while IL-17B and IL-17F are angiogenesis inhibitors. Recently, IL-17A/F heterodimer, comprised of the IL-17A and IL-17F subunits, was found as another member of the IL-17 cytokine family. However, to date, it has been unknown whether IL-17A/F has biological actions to affect the angiogenesis-related vascular endothelial functions...
2016: Tohoku Journal of Experimental Medicine
Hsu-Tung Lee, Hao-Teng Chang, Sophie Lee, Chen-Huan Lin, Jia-Rong Fan, Shinn-Zong Lin, Chung Y Hsu, Chia-Hung Hsieh, Woei-Cherng Shyu
To guide the use of human mesenchymal stem cells (MSCs) toward clinical applications, identifying pluripotent-like-markers for selecting MSCs that retain potent self-renewal-ability should be addressed. Here, an insulin-like growth factor 1 receptor (IGF1R)-expressing sub-population in human dental pulp MSCs (hDSCs), displayed multipotent properties. IGF1R expression could be maintained in hDSCs when they were cultured in 2% human cord blood serum (hUCS) in contrast to that in 10% fetal calf serum (FCS). Cytokine array showed that hUCS contained higher amount of several growth factors compared to FCS, including IGF-1 and platelet-derived growth factor (PDGF-BB)...
2016: Scientific Reports
Benjamin Heyman, Yiping Yang
Heparanase is an endo-β-D-glucuronidase capable of cleaving heparan sulfate (HS) side chains contributing to break down of the extracellular matrix. Increased expression of heparanase has been found in numerous malignancies, and is associated with a poor prognosis. It has generated significant interest as a potential anti-neoplastic target because of the multiple roles it plays in tumor growth and metastasis. The pro-tumorigenic effects of heparanase are enhanced by the release of HS side chains, with subsequent increase in bioactive fragments and increased cytokine levels; both promoting tumor invasion, angiogenesis and metastasis...
August 26, 2016: Experimental Hematology
Norio Kubo, Kenichiro Araki, Hiroyuki Kuwano, Ken Shirabe
The hepatic stellate cells in the liver are stimulated sustainably by chronic injury of the hepatocytes, activating myofibroblasts, which produce abundant collagen. Myofibroblasts are the major source of extracellular proteins during fibrogenesis, and may directly, or secreted products, contribute to carcinogenesis and tumor progression. Cancer-associated fibroblasts (CAFs) are one of the components of the tumor microenvironment that promote the proliferation and invasion of cancer cells by secreting various growth factors and cytokines...
August 14, 2016: World Journal of Gastroenterology: WJG
Efstathios A Antoniou, Ioannis Koutsounas, Christos Damaskos, Sotiris Koutsounas
BACKGROUND: Psoriasis is a chronic, immune-mediated and angiogenesis-dependent disease. Activated keratinocytes in psoriatic lesions produce pro-angiogenic cytokines, including vascular endothelial growth factor (VEGF), which binds to vascular endothelial growth factor receptor (VEGFR) and promotes cell proliferation and angiogenesis. Sorafenib (BAY 43-9006) is a molecular multikinase inhibitor of RAF kinase, platelet-derived growth factor (PDGF), VEGFR-1, -2, -3, platelet-derived growth factor receptor (PDGFR)-β and c-Kit...
September 2016: In Vivo
Pablo F Barcelona, Nicholas Sitaras, Alba Galan, Gema Esquiva, Sean Jmaeff, Yifan Jian, Marinko V Sarunic, Nicolas Cuenca, Przemyslaw Sapieha, H Uri Saragovi
UNLABELLED: In many diseases, expression and ligand-dependent activity of the p75(NTR) receptor can promote pericyte and vascular dysfunction, inflammation, glial activation, and neurodegeneration. Diabetic retinopathy (DR) is characterized by all of these pathological events. However, the mechanisms by which p75(NTR) may be implicated at each stage of DR pathology remain poorly understood. Using a streptozotocin mouse model of diabetic retinopathy, we report that p75(NTR) is upregulated very early in glia and in pericytes to mediate ligand-dependent induction of inflammatory cytokines, disruption of the neuro-glia-vascular unit, promotion of blood-retina barrier breakdown, edema, and neuronal death...
August 24, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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