scholarly journals Inhibition of Cyclooxygenase-2 Alters Craniofacial Patterning during Early Embryonic Development of Chick

2021 ◽  
Vol 9 (2) ◽  
pp. 16
Author(s):  
Bhaval Parmar ◽  
Urja Verma ◽  
Kashmira Khaire ◽  
Dhanush Danes ◽  
Suresh Balakrishnan
Keyword(s):  
Embryonic Development ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Neural Crest Cell ◽  
Cyclooxygenase 2 ◽  
Nuclear Antigen ◽  
Chick Embryos ◽  
Downstream Effector ◽  
Cox 2 ◽  
And Migration

A recent study from our lab revealed that the inhibition of cyclooxygenase-2 (COX-2) exclusively reduces the level of PGE2 (Prostaglandin E2) among prostanoids and hampers the normal development of several structures, strikingly the cranial vault, in chick embryos. In order to unearth the mechanism behind the deviant development of cranial features, the expression pattern of various factors that are known to influence cranial neural crest cell (CNCC) migration was checked in chick embryos after inhibiting COX-2 activity using etoricoxib. The compromised level of cell adhesion molecules and their upstream regulators, namely CDH1 (E-cadherin), CDH2 (N-cadherin), MSX1 (Msh homeobox 1), and TGF-β (Transforming growth factor beta), observed in the etoricoxib-treated embryos indicate that COX-2, through its downstream effector PGE2, regulates the expression of these factors perhaps to aid the migration of CNCCs. The histological features and levels of FoxD3 (Forkhead box D3), as well as PCNA (Proliferating cell nuclear antigen), further consolidate the role of COX-2 in the migration and survival of CNCCs in developing embryos. The results of the current study indicate that COX-2 plays a pivotal role in orchestrating craniofacial structures perhaps by modulating CNCC proliferation and migration during the embryonic development of chicks.

scholarly journals Inhibition of Cyclooxygenase-2 Alters Cranial Neural Crest Cell Migration in the Developing chick

2021 ◽  
Author(s):  
Bhaval Parmar ◽  
Urja Verma ◽  
Kashmira Khaire ◽  
Dhanush Danes ◽  
Suresh Balakrishnan
Keyword(s):  
Neural Crest ◽  
Neural Crest Cell ◽  
Cyclooxygenase 2 ◽  
Cranial Neural Crest ◽  
Downstream Effector ◽  
Cranial Neural Crest Cell ◽  
Neural Crest Cell Migration ◽  
Cox 2 ◽  
And Migration ◽  
Crest Cell

A recent study from our lab revealed that inhibition of cyclooxygenase-2 exclusively reduces the level of PGE2 amongst the prostanoids and hamper the normal development of several structures, strikingly the cranial vault, in chick embryos. In order to unearth the mechanism behind the deviant development of cranial features, the expression pattern of various factors that are known to influence the cranial neural crest cell (CNCC) migration were checked in chick embryo after inhibiting the COX-2 activity using etoricoxib. The compromised level of cell adhesion molecules and their upstream regulators, namely CDH1, CDH2, MSX1, and TGF-β, observed in the etoricoxib treated embryos indicate that COX-2, through its downstream effector PGE2, regulates the expression of these factors perhaps to aid the migration of CNCC. The histological features and levels of FoxD3 as well as PCNA further consolidates the role of COX-2 in migration and survival of CNCC in developing embryo. The results of the current study indicate that the COX-2 plays a pivotal role in orchestrating the proliferation and migration of CNCC during embryonic development of chick.

Intracisternal administration of transforming growth factor-β evokes fever through the induction of cyclooxygenase-2 in brain endothelial cells

2008 ◽  
Vol 294 (1) ◽  
pp. R266-R275 ◽  
Author(s):  
Shigenobu Matsumura ◽  
Tetsuro Shibakusa ◽  
Teppei Fujikawa ◽  
Hiroyuki Yamada ◽  
Kiyoshi Matsumura ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Proinflammatory Cytokines ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Cyclooxygenase 2 ◽  
Dependent Manner ◽  
Cox 2 ◽  
Β Receptor

Transforming growth factor-β (TGF-β), a pleiotropic cytokine, regulates cell proliferation, differentiation, and apoptosis, and plays a key role in development and tissue homeostasis. TGF-β functions as an anti-inflammatory cytokine because it suppresses microglia and B-lymphocyte functions, as well as the production of proinflammatory cytokines. However, we previously demonstrated that the intracisternal administration of TGF-β induces fever like that produced by proinflammatory cytokines. In this study, we investigated the mechanism of TGF-β-induced fever. The intracisternal administration of TGF-β increased body temperature in a dose-dependent manner. Pretreatment with cyclooxygenase-2 (COX-2)-selective inhibitor significantly suppressed TGF-β-induced fever. COX-2 is known as one of the rate-limiting enzymes of the PGE2 synthesis pathway, suggesting that fever induced by TGF-β is COX-2 and PGE2 dependent. TGF-β increased PGE2 levels in cerebrospinal fluid and increased the expression of COX-2 in the brain. Double immunostaining of COX-2 and von Willebrand factor (vWF, an endothelial cell marker) revealed that COX-2-expressing cells were mainly endothelial cells. Although not all COX-2-immunoreactive cells express TGF-β receptor, some COX-2-immunoreactive cells express activin receptor-like kinase-1 (ALK-1, an endothelial cell-specific TGF-β receptor), suggesting that TGF-β directly or indirectly acts on endothelial cells to induce COX-2 expression. These findings suggest a novel function of TGF-β as a proinflammatory cytokine in the central nervous system.

scholarly journals Transforming growth factor beta regulates cyclooxygenase-2 in glomerular mesangial cells

2006 ◽  
Vol 69 (9) ◽  
pp. 1578-1585 ◽  
Author(s):  
P. Harding ◽  
L. Balasubramanian ◽  
J. Swegan ◽  
A. Stevens ◽  
W.F. Glass
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Mesangial Cells ◽  
Cyclooxygenase 2 ◽  
Glomerular Mesangial Cells ◽  
Growth Factor Beta

Platelet-derived growth factor BB modulates PCNA protein synthesis partially through the transforming growth factor beta signalling pathway in vascular smooth muscle cells

2007 ◽  
Vol 85 (5) ◽  
pp. 606-615 ◽  
Author(s):  
Dabin Pan ◽  
Junwei Yang ◽  
Fengxiang Lu ◽  
Di Xu ◽  
Lei Zhou ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Vascular Smooth Muscle ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Platelet Derived Growth Factor ◽  
Nuclear Antigen ◽  
Type I ◽  
Signalling System ◽  
Alk 5

PDGF-BB (Platelet-derived growth factor BB) and TGF-β1(transforming growth factor β1) are important growth factors in the modulation of vascular smooth muscle cell (VSMC) proliferation and PCNA (proliferating cell nuclear antigen) expression in VSMCs. PCNA expresses at a high level in proliferating cells. The present study aims to assess the effects of PDGF-BB-induced overexpression of TGF-β1 on PCNA in VSMCs. The downstream proteins of the TGF-β signalling system in VSMCs, including TGF-β type I receptor (ALK-5 in VSMCs), Smurf2, Smad2, pSmad2/3, Smad4, and Smad7, were also investigated. Our results revealed that PDGF-BB significantly increased the expressions of TGF-β1 and PCNA, and the increase in PCNA can be partially inhibited by neutralizing anti-TGF-β1 antibody. Furthermore, PDGF-BB increased the expression of ALK-5, Smurf2, pSmad2/3, and Smad4, but lowered the levels of Smad2 and Smad7; these alterations were partially restored by neutralizing anti-TGF-β1 antibody. These findings suggest that PDGF-BB promotes PCNA expression in VSMCs partially through TGF-β1 overexpression, and that the TGF-β signalling system involves the molecular mechanism of PDGF-BB in VSMCs.

Transforming growth factor-beta — mediator of carcinogenesis, inflammation and embryonic development

1988 ◽  
Vol 330 (4-5) ◽  
pp. 308-308
Author(s):  
Kathleen C. Flanders ◽  
Ursula I. Heine ◽  
Nancy L. Thompson ◽  
Lalage M. Wakefield ◽  
Michael B. Sporn ◽  
...  
Keyword(s):  
Growth Factor ◽  
Embryonic Development ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Growth Factor Beta

scholarly journals Chlorophenyl-benzoxime inhibits pancreatic cancer cell proliferation, invasion and migration by down-regulating the expressions of interleukin-8 and cyclooxygenase-2

2021 ◽  
Vol 18 (7) ◽  
pp. 1413-1418
Author(s):  
Pinyan Wang ◽  
Yanan Xue ◽  
Xiao Yu
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Western Blotting ◽  
Mtt Assay ◽  
Quantitative Polymerase Chain Reaction ◽  
Cyclooxygenase 2 ◽  
Interleukin 8 ◽  
Invasion And Migration ◽  
Cox 2 ◽  
And Migration

Purpose: To investigate the effects of chlorophenyl-benzoxime (CPBZX) on pancreatic cancer (PC) cell proliferation, invasion and migration, and the underlying mechanism of action. Methods: Pancreatic carcinoma cell lines (HuP-T4, HuP-T3 and BxPC-3) were cultured in Dulbecco's Modified Eagle medium (DMEM) containing 10 % fetal bovine serum (FBS), penicillin (100 U/mL) and streptomycin (10 μg/mL) at 37 ˚C in a humidified atmosphere containing 5 % CO2 and 95 % air. Cell proliferation was assessed using MTT assay. Real-time quantitative polymerase chain reaction (qRTPCR) and Western blotting were employed for the determination of changes in the levels of expression of carcinoembryonic antigen (CEA), interleukin-8 (IL-8) and cyclooxygenase-2 (COX 2). Cell invasion and migration were determined using Transwell and wound healing assays, respectively. Results: The results of MTT assay showed that CPBZX significantly and dose-dependently inhibited the proliferation of PC cells (p < 0.05). Incubation of HuP-T4 cells with CPBZX significantly and dosedependently reduced the invasive ability of the cells (p < 0.05). The migratory ability of HuP-T4 cells was also significantly and dose-dependently inhibited by CPBZX (p < 0.05). The results of Western blotting and qRT PCR showed that CPBZX treatment significantly and dose-dependently upregulated CEA mRNA expression (p < 0.05). On the other hand, the expressions of IL-8 and COX-2 were significantly and dose-dependently down-regulated by CPBZX. Treatment of pancreatic tumor mice with CPBZX significantly decreased tumor growth and metastasis of tumor cells to the pulmonary tissues, liver and lymph nodes (p < 0.05). Conclusion: The results of this study suggest that CPBZX inhibits the development and metastasis of PC via the down-regulation of IL-8 and COX 2 expressions, and therefore may find application in pancreatic cancer therapy.

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