Coordinate expression of secretory phospholipase A2 and cyclooxygenase-2 in activated human keratinocytes

2000 ◽  
Vol 278 (4) ◽  
pp. C822-C833 ◽  
Author(s):  
Krystyna E. Rys-Sikora ◽  
Raymond L. Konger ◽  
John W. Schoggins ◽  
Rama Malaviya ◽  
Alice P. Pentland
Keyword(s):  
Wound Repair ◽  
Human Keratinocytes ◽  
Plating Density ◽  
Coordinate Expression ◽  
Cox 2 ◽  
Type V ◽  
In Vitro Wounding

PGE2 levels are altered in human epidermis after in vivo wounding; however, mechanisms modulating PGE2 production in activated keratinocytes are unclear. In previous studies, we showed that PGE2 is a growth-promoting autacoid in human primary keratinocyte cultures, and its production is modulated by plating density, suggesting that regulated PGE2 synthesis is an important component of wound healing. Here, we examine the role of phospholipase A2(PLA2) and cyclooxygenase (COX) enzymes in modulation of PGE2 production. We report that the increased PGE2 production that occurs in keratinocytes grown in nonconfluent conditions is also observed after in vitro wounding, indicating that similar mechanisms are involved. This increase was associated with coordinate upregulation of both COX-2 and secretory PLA2 (sPLA2) proteins. Increased sPLA2 activity was also observed. By RT-PCR, we identified the presence of type IIA and type V sPLA2, along with the M-type sPLA2 receptor. Thus the coordinate expression of sPLA2 and COX-2 may be responsible for the increased prostaglandin synthesis in activated keratinocytes during wound repair.

scholarly journals The Role of Propolis in Pulp Pain by Inhibiting Cyclooxygenase-2 Expression

2021 ◽  
Vol 11 (1) ◽  
pp. 11
Author(s):  
Ira Widjiastuti ◽  
Widya Saraswati ◽  
Annisa Rahma
Keyword(s):  
Side Effects ◽  
Pain Relief ◽  
Inflammatory Pain ◽  
Cyclooxygenase 2 ◽  
Propolis Extract ◽  
In Silico Studies ◽  
Cox 2

Background: Inflammation of the pulp can lead to elicit pain. Pain in inflammation is induced by the cyclooxygenase-2 enzyme (COX-2) which induces prostaglandin E2 (PGE2) resulting in pain. Pain in the pulp can be relieved by eugenol. In its application, eugenol is toxic to pulp fibroblasts. Due to the side effect, it is worth considering other biocompatible materials with minimal side effects, such as propolis. Flavonoids and phenolic acids that contained in propolis can inhibit COX-2. Therefore, an analysis outlined in the literature review is needed to examine the results of research related to the role of propolis as pulp pain relief by inhibiting COX-2 expression. Purpose: To analyze the role of propolis in pulp pain by inhibiting COX-2 expression. Reviews: Propolis extract that extracted by ethanol, water, and hydroalcohol has pain relief properties in the pulp by inhibiting COX-2 by directly binding to the COX-2 receptors and by reducing the production of proinflammatory cytokines which are COX-2 inducers, proven through in vivo, in vitro, and in silico studies in various target cell organs. Conclusion: Propolis extract has high prospect as inflammatory pain inhibitor in the pulp by inhibit COX-2 expression.

scholarly journals COX-2 mediates angiotensin II-induced (pro)renin receptor expression in the rat renal medulla

2014 ◽  
Vol 307 (1) ◽  
pp. F25-F32 ◽  
Author(s):  
Fei Wang ◽  
Xiaohan Lu ◽  
Kexin Peng ◽  
Li Zhou ◽  
Chunling Li ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Protein Expression ◽  
Renal Medulla ◽  
Receptor Expression ◽  
Ang Ii ◽  
Cox 2 ◽  
Renin Content

(Pro)renin receptor (PRR) is predominantly expressed in the distal nephron where it is activated by angiotensin II (ANG II), resulting in increased renin activity in the renal medulla thereby amplifying the de novo generation and action of local ANG II. The goal of the present study was to test the role of cycloxygenase-2 (COX-2) in meditating ANG II-induced PRR expression in the renal medulla in vitro and in vivo. Exposure of primary rat inner medullary collecting duct cells to ANG II induced sequential increases in COX-2 and PRR protein expression. When the cells were pretreated with a COX-2 inhibitor NS-398, ANG II-induced upregulation of PRR protein expression was almost completely abolished, in parallel with the changes in medium active renin content. The inhibitory effect of NS-398 on the PRR expression was reversed by adding exogenous PGE2. A 14-day ANG II infusion elevated renal medullary PRR expression and active and total renin content in parallel with increased urinary renin, all of which were remarkably suppressed by the COX-2 inhibitor celecoxib. In contrast, plasma and renal cortical active and total renin content were suppressed by ANG II treatment, an effect that was unaffected by COX-2 inhibition. Systolic blood pressure was elevated with ANG II infusion, which was attenuated by the COX-2 inhibition. Overall, the results obtained from in vitro and in vivo studies established a crucial role of COX-2 in mediating upregulation of renal medullary PRR expression and renin content during ANG II hypertension.

scholarly journals Inhibition of Calcineurin/NFAT Signaling Blocks Oncogenic H-Ras Induced Autophagy in Primary Human Keratinocytes

2021 ◽  
Vol 9 ◽  
Author(s):  
Shuangshuang Wang ◽  
Hua Qian ◽  
Liwei Zhang ◽  
Panpan Liu ◽  
Dexuan Zhuang ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
Human Keratinocytes ◽  
Primary Human Keratinocytes ◽  
Activated T Cells ◽  
Ras Pathway ◽  
Ras Family ◽  
Interfering Rna

Mutations of H-Ras, a member of the RAS family, are preferentially found in cutaneous squamous cell carcinomas (SCCs). H-Ras has been reported to induce autophagy, which plays an essential role in tissue homeostasis in multiple types of cancer cells and in fibroblasts, however, the potential role of H-Ras in regulating autophagy in human keratinocytes has not been reported. In this study, we found that the stable expression of the G12V mutant of H-RAS (H-RasG12V) induced autophagy in human keratinocytes, and interestingly, the induction of autophagy was strongly blocked by inhibiting the calcineurin/nuclear factor of activated T cells (NFAT) pathway with either a calcineurin inhibitor (Cyclosporin A) or a NFAT inhibitor (VIVIT), or by the small interfering RNA (siRNA) mediated knockdown of calcineurin B1 or NFATc1 in vitro, as well as in vivo. To characterize the role of the calcineurin/NFAT pathway in H-Ras induced autophagy, we found that H-RasG12V promoted the nuclear translocation of NFATc1, an indication of the activation of the calcineurin/NFAT pathway, in human keratinocytes. However, activation of NFATc1 either by the forced expression of NFATc1 or by treatment with phenformin, an AMPK activator, did not increase the formation of autophagy in human keratinocytes. Further study revealed that inhibiting the calcineurin/NFAT pathway actually suppressed H-Ras expression in H-RasG12V overexpressing cells. Finally, chromatin immunoprecipitation (ChIP) assays showed that NFATc1 potentially binds the promoter region of H-Ras and the binding efficiency was significantly enhanced by the overexpression of H-RasG12V, which was abolished by treatment with the calcineurin/NFAT pathway inhibitors cyclosporine A (CsA) or VIVIT. Taking these data together, the present study demonstrates that the calcineurin/NFAT signaling pathway controls H-Ras expression and interacts with the H-Ras pathway, involving the regulation of H-Ras induced autophagy in human keratinocytes.

scholarly journals Endotoxin induces proliferation of NSCLC in vitro and in vivo: role of COX-2 and EGFR activation

2012 ◽  
Vol 62 (2) ◽  
pp. 309-320 ◽  
Author(s):  
Katja Hattar ◽  
Rajkumar Savai ◽  
Florentine S. B. Subtil ◽  
Jochen Wilhelm ◽  
Anja Schmall ◽  
...  
Keyword(s):  
Egfr Activation ◽  
Cox 2

A crucial role of β1 integrins for keratinocyte migration in vitro and during cutaneous wound repair

Development ◽  
2002 ◽  
Vol 129 (9) ◽  
pp. 2303-2315 ◽  
Author(s):  
Richard Grose ◽  
Caroline Hutter ◽  
Wilhelm Bloch ◽  
Irmgard Thorey ◽  
Fiona M. Watt ◽  
...  
Keyword(s):  
Crucial Role ◽  
Wound Repair ◽  
Proliferation Rate ◽  
Cutaneous Wound ◽  
Keratinocyte Migration ◽  
Β1 Integrins ◽  
Cell Matrix Interactions

Integrins are ubiquitous transmembrane receptors that play crucial roles in cell-cell and cell-matrix interactions. In this study, we have determined the effects of the loss of β1 integrins in keratinocytes in vitro and during cutaneous wound repair. Flow cytometry of cultured β1-deficient keratinocytes confirmed the absence of β1 integrins and showed downregulation of α6β4 but not of αv integrins. β1-null keratinocytes were characterised by poor adhesion to various substrates, by a reduced proliferation rate and by a strongly impaired migratory capacity. In vivo, the loss of β1 integrins in keratinocytes caused a severe defect in wound healing. β1-null keratinocytes showed impaired migration and were more densely packed in the hyperproliferative epithelium. Surprisingly, their proliferation rate was not reduced in early wounds and even increased in late wounds. The failure in re-epithelialisation resulted in a prolonged inflammatory response, leading to dramatic alterations in the expression of important wound-regulated genes. Ultimately, β1-deficient epidermis did cover the wound bed, but the epithelial architecture was abnormal. These findings demonstrate a crucial role of β1 integrins in keratinocyte migration and wound re-epithelialisation. Movies available on-line

Regulation of prostaglandin biosynthesis in vivo by glutathione

1998 ◽  
Vol 274 (2) ◽  
pp. R294-R302 ◽  
Author(s):  
Alon Margalit ◽  
Scott D. Hauser ◽  
Ben S. Zweifel ◽  
Melissa A. Anderson ◽  
Peter C. Isakson
Keyword(s):  
Reduced Glutathione ◽  
Intraperitoneal Administration ◽  
Peritoneal Macrophages ◽  
Urate Crystal ◽  
Cox 2 ◽  
Cox 1 ◽  
Urate Crystals

Intraperitoneal administration of urate crystals to mice reduced subsequent macrophage conversion of arachidonic acid (AA) to prostaglandins (PGs) and 12-hydroxyeicosatetraenoic acid for up to 6 h. In contrast, levels of 12-hydroxyheptadecatrienoic acid (12-HHT) were markedly elevated. This metabolic profile was previously observed in vitro when recombinant cyclooxygenase (COX) enzymes were incubated with reduced glutathione (GSH). Analysis of peritoneal GSH levels revealed a fivefold elevation after urate crystal administration. The GSH synthesis inhibitorl-buthionine-[ S, R]-sulfoximine partially reversed the urate crystal effect on both GSH elevation and PG synthesis. Moreover, addition of exogenous GSH to isolated peritoneal macrophages shifted AA metabolism from PGs to 12-HHT. Urate crystal administration reduced COX-1, but induced COX-2 expression in peritoneal cells. The reduction of COX-1 may contribute to the attenuation of PG synthesis after 1 and 2 h, but PG synthesis remained inhibited up to 6 h, when COX-2 levels were high. Overall, our results indicate that elevated GSH levels inhibit PG production in this model and provide in vivo evidence for the role of GSH in the regulation of PG biosynthesis.

scholarly journals The role of the interferon regulatory factors, IRF-1 and IRF-2, in LPS-induced cyclooxygenase-2 (COX-2) expression in vivo and in vitro

2002 ◽  
Vol 8 (5) ◽  
pp. 381-390 ◽  
Author(s):  
Shuling Zhang ◽  
Karen Thomas ◽  
Jorge C.G. Blanco ◽  
Cindy A. Salkowski ◽  
Stefanie N. Vogel
Keyword(s):  
Cyclooxygenase 2 ◽  
Regulatory Factors ◽  
Interferon Regulatory Factors ◽  
Cox 2

The role of oxidised regenerated cellulose/collagen in wound repair: effects in vitro on fibroblast biology and in vivo in a model of compromised healing

2002 ◽  
Vol 34 (12) ◽  
pp. 1557-1570 ◽  
Author(s):  
Jeffrey Hart ◽  
Derek Silcock ◽  
Stephen Gunnigle ◽  
Breda Cullen ◽  
Nicholas D Light ◽  
...  
Keyword(s):  
Wound Repair ◽  
Regenerated Cellulose

The role of the interferon regulatory factors, IRF-1 and IRF-2, in LPS-induced cyclooxygenase-2 (COX-2) expression in vivo and in vitro

2002 ◽  
Vol 8 (5) ◽  
pp. 379-388 ◽  
Author(s):  
Shuling Zhang ◽  
Karen Thomas ◽  
Jorge C. G. Blanco ◽  
Cindy A. Salkowski ◽  
Stefanie N. Vogel
Keyword(s):  
Cyclooxygenase 2 ◽  
Regulatory Factors ◽  
Interferon Regulatory Factors ◽  
Cox 2

scholarly journals Gentiana lutea Extract Modulates Ceramide Synthesis in Primary and Psoriasis-Like Keratinocytes

Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1832
Author(s):  
Fabian Gendrisch ◽  
Anna Nováčková ◽  
Michaela Sochorová ◽  
Birgit Haarhaus ◽  
Kateřina Vávrová ◽  
...  
Keyword(s):  
Skin Diseases ◽  
Human Keratinocytes ◽  
Ceramide Synthase ◽  
Gentiana Lutea ◽  
Tnf Α ◽  
Ceramide Synthesis ◽  
Ceramide Content

Gentiana lutea is a bitter herb that is traditionally used to improve gastric disorders. Recently, we have shown that Gentiana lutea extract (GE) also modulates the lipid metabolism of human keratinocytes in vitro and in vivo. In the present study, we investigated the role of GE on ceramide synthesis in human primary keratinocytes (HPKs) and psoriasis-like keratinocytes. We could demonstrate that GE increased the concentrations of glucosylceramides and the ceramide AS/AdS subclass without affecting the overall ceramide content in HPKs. The expression of ceramide synthase 3 (CERS3) and elongases (ELOVL1 and 4) was reduced in psoriasis lesions compared to healthy skin. Psoriasis-like HPKs, generated by stimulating HPKs with cytokines that are involved in the pathogenesis of psoriasis (IL-17, TNF-α, IL-22 and IFN-γ) showed increased levels of IL-6, IL-8 and increased expression of DEFB4A, as well as decreased expression of ELOVL4. The treatment with GE partly rescued the reduced expression of ELOVL4 in psoriasis-like HPKs and augmented CERS3 expression. This study has shown that GE modulates ceramide synthesis in keratinocytes. Therefore, GE might be a novel topical treatment for skin diseases with an altered lipid composition such as psoriasis.

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