Interleukin-1 Beta Promotes the Expression of Prox-1 and Vascular Endothelial Growth Factor Receptor Type-3 in Adult Human Dermal Fibroblasts

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4738-4738
Author(s):  
Matsuo Takuji ◽  
Ryosuke Shirasaki ◽  
Haruko Tashiro ◽  
Yoko Oka ◽  
Tadashi Yamamoto ◽  
...  

Abstract Abstract 4738 Background and Aims: We recently reported that human interleukin 1 beta (IL-1 beta) stimulates bone-marrow stromal myofibroblasts to express a hematopoietic stem cell marker, CD34 (16th EHA, and 53rdASH meeting). To characterize precisely the effects of IL-1 beta to the stromal cells, adult human dermal fibroblasts (HDF) were cultured with IL-1 beta, and the morphological changes and molecular expressions were observed. Materials and Methods: HDF were purchased, and cultured in knockout DMEM medium with 15% KSR with or without recombinant human IL-1 beta for 3 weeks. The morphological changes and the expression of specific hematopoiesis-related genes were analyzed time-dependently. The concentration of hematopoietic growth factors in the culturing supernatants was also measured. Results: When HDF were cultured with human IL-1 beta for 3 weeks, the cellular morphology changed to the filamentous appearance. RT-PCR analyses revealed that cells expressed Prox-1, a master molecule for lymphatic duct neogenesis, and also vascular endothelial growth factor receptor (VEGFR) type-3. Smad7 and PAI1 were also expressed; however, LYVE1, a marker for lymphatic vascular endothelial cell, was not induced. VEGF-C production was also demonstrated at RNA and protein levels, and VEGF-C and VEGFR type-3 system played an important role in morphological changes and cell-proliferation. Discussion: We previously reported that when HDF were cultured in DMEM/F12 medium with IL-1 beta and EPO, hematopoietic markers were induced. When HDF were cultured in knockout DMEM, a condition for immature cell-growth at ES cell levels, and IL-1 beta, lymphatic duct neogenesis-related genes were activated, and HDF converted their morphology without an introduction of any genes externally. We are now making clear the precise action of IL-1 beta to HDF using microarray analysis. Disclosures: No relevant conflicts of interest to declare.

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Hülya Çevik-Aras ◽  
Fadimana Isik-Altun ◽  
Hatice Kilic-Tok ◽  
Julia Naoumova

Background and Objective. Vascular endothelial growth factor (VEGF) and interleukin 1 beta (IL-1β) perform functions in orthodontic tooth movement and can be measured in the saliva. This novel approach is aimed at monitoring continuous changes in IL-1β and VEGF levels in saliva during two years of orthodontic treatment. Material and Methods. Nine healthy females (15-20 years of age) with crowding requiring four premolar extractions and fixed appliances in both jaws were included in this prospective pilot study. A total of 134 stimulated and 134 unstimulated saliva samples were collected during two years of treatment: before tooth extractions (baseline) and then every 6-8 weeks at follow-up appointments. All saliva samples were analysed by the enzyme-linked immunosorbent assay. The mean levels of IL-1β and VEGF were calculated according to the different orthodontic treatment stages: alignment, space closure, and finishing. Repeated analysis of variance (ANOVA) measurements were used to compare the means between different treatment stages. The percentage difference in IL-1β and VEGF between the different treatment stages was analysed by Bland-Altman plots. Results. A gradual increase in IL-1β and VEGF was observed at alignment, reaching significance at space closure ( p = 0.002 and p = 0.025 , respectively). At finishing, both IL-1β and VEGF declined, however, without reverting to baseline values ( p = 0.172 and p = 0.207 , respectively). Bland-Altman analysis showed the agreement between IL-1β and VEGF in terms of a systematic increase, with a higher percentage difference for VEGF. Conclusions. The salivary levels of both IL-1β and VEGF increased following orthodontic treatment and reached their peaks during the treatment stage of space closure. This novel approach provides a hint on how and when to sample saliva during orthodontic treatment to analyse bone remodelling.


2012 ◽  
Vol 03 (02) ◽  
pp. 93-92
Author(s):  
Alexander Kretzschmar

Vandetanib ist ein oraler Hemmer des RET-Kinase-, VEGF (Vascular Endothelial Growth Factor Receptor)- und EGFR (Epidermal Growth Factor Receptor)-Signalwegs. In einer zulassungsrelevanten, randomisierten, doppelblinden, placebokontrollierten Phase- III-Studie verlängerte der Tyrosinkinasehemmer das progressionsfreie Überleben (PFS) signifikant länger als Placebo.


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