Cyclooxygenase-2-regulated vascular endothelial growth factor release in gastric fibroblasts

VEGF is a highly specific stimulator of endothelial cells and may play an important role in angiogenesis in the process of tissue regeneration. We previously showed that cyclooxygenase-2 (COX-2) expressed in mesenchymal cells of the ulcer bed is involved in the ulcer repair process. To clarify the role of COX-2 in angiogenesis during gastric ulcer healing, we investigated the relation between COX-2 expression and VEGF production in human gastric fibroblasts in vivo and in vitro. Gastric fibroblasts were cultured in RPMI 1640 with and without IL-1α or IL-1β in the presence or absence of NS-398, a selective COX-2 inhibitor. Supernatant VEGF and PGE2 concentrations were measured by enzyme-linked immunosorbent assay. COX-2 expression in fibroblasts was determined by Western blot analysis. VEGF and COX-2 expression in surgical resections of human gastric ulcer tissue was examined immunohistochemically. IL-1 dose dependently enhanced VEGF release in cultured gastric fibroblasts after a 24-h stimulation. IL-1 also stimulated PGE2 production in gastric fibroblasts via COX-2 induction. NS-398 significantly suppressed VEGF and PGE2 release from IL-1-stimulated gastric fibroblasts; concurrent addition of PGE2 restored NS-398-inhibited VEGF release. COX-2 and VEGF immunoreactivity were colocalized in fibroblast-like cells in the ulcer bed of gastric tissues. These results suggest that COX-2 plays a key role in VEGF production in gastric fibroblasts stimulated by IL-1 in vitro and that angiogenesis induced by the COX-2-VEGF pathway might be involved in gastric ulcer healing.

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The Possible Role of Vascular Endothelial Growth Factor (VEGF) in Gastric Ulcer Healing: Effect of Sofalcone on VEGF Release In Vitro

Journal of Clinical Gastroenterology ◽

10.1097/00004836-199800001-00029 ◽

1998 ◽

Vol 27 ◽

pp. S178-S182 ◽

Cited By ~ 9

Author(s):

Morio Takahashi ◽

Shin Maeda ◽

Keiji Ogura ◽

Akira Terano ◽

Masao Omata

Keyword(s):

Vascular Endothelial Growth Factor ◽

Gastric Ulcer ◽

Growth Factor ◽

Ulcer Healing ◽

Vascular Endothelial ◽

Gastric Ulcer Healing ◽

Endothelial Growth Factor ◽

Vegf Release

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Evidence of gastric ulcer healing activity of Maytenus robusta Reissek: In vitro and in vivo studies

Journal of Ethnopharmacology ◽

10.1016/j.jep.2015.09.006 ◽

2015 ◽

Vol 175 ◽

pp. 75-85 ◽

Cited By ~ 31

Author(s):

Luisa Mota da Silva ◽

Thaise Boeing ◽

Lincon Bordignon Somensi ◽

Benhur Judah Cury ◽

Viviane Miranda Bispo Steimbach ◽

...

Keyword(s):

Gastric Ulcer ◽

Ulcer Healing ◽

In Vivo Studies ◽

Gastric Ulcer Healing

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Chronic gastric ulcer healing in rats subjected to selective and non-selective cyclooxygenase-2 inhibitors

European Journal of Pharmacology ◽

10.1016/s0014-2999(02)01494-2 ◽

2002 ◽

Vol 442 (1-2) ◽

pp. 125-135 ◽

Cited By ~ 24

Author(s):

Bettina Berenguer ◽

Catalina Alarcón de la Lastra ◽

Francisco Javier Moreno ◽

Maria José Martı́n

Keyword(s):

Gastric Ulcer ◽

Ulcer Healing ◽

Cyclooxygenase 2 ◽

Chronic Gastric Ulcer ◽

Gastric Ulcer Healing ◽

Cyclooxygenase 2 Inhibitors

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Role of nuclear factor-κB in gastric ulcer healing in rats

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.2001.280.6.g1296 ◽

2001 ◽

Vol 280 (6) ◽

pp. G1296-G1304 ◽

Cited By ~ 15

Author(s):

Satoru Takahashi ◽

Takuya Fujita ◽

Akira Yamamoto

Keyword(s):

Gastric Ulcer ◽

Mrna Expression ◽

Ulcer Healing ◽

Nuclear Factor Κb ◽

Normal Mucosa ◽

Cyclooxygenase 2 ◽

Interleukin 1Β ◽

Nuclear Factor ◽

Gastric Ulcer Healing

We investigated the role of nuclear factor-κB (NF-κB) in gastric ulcer healing in rats. NF-κB was activated in ulcerated tissue but not in normal mucosa, and the level of the activation was decreased with ulcer healing. NF-κB activation was observed in fibroblasts, monocytes/macrophages, and neutrophils. Treatment of gastric fibroblasts, isolated from the ulcer base, with interleukin-1β activated NF-κB and the subsequently induced cyclooxygenase-2 and cytokine-induced neutrophil chemoattractant-1 (CINC-1) mRNA expression. Inhibition of activated NF-κB action resulted in suppression of both their mRNA expression and increases in PGE2 and CINC-1 levels induced by interleukin-1β. Persistent prevention of NF-κB activation caused an impairment of ulcer healing in rats. Gene expression of interleukin-1β, CINC-1, cyclooxygenase-2, and inducible nitric oxide synthase in ulcerated tissue had been inhibited before the delay in ulcer healing became manifest. The increased levels of cyclooxygenase-2 protein and PGE2 production were also reduced. These results demonstrate that NF-κB, activated in ulcerated tissue, might upregulate the expression of healing-promoting factors responsible for gastric ulcer healing in rats.

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Ellagic acid facilitates indomethacin-induced gastric ulcer healing via COX-2 up-regulation

Acta Biochimica et Biophysica Sinica ◽

10.1093/abbs/gms034 ◽

2012 ◽

Vol 44 (7) ◽

pp. 565-576 ◽

Cited By ~ 29

Author(s):

A. Chatterjee ◽

S. Chatterjee ◽

S. Das ◽

A. Saha ◽

S. Chattopadhyay ◽

...

Keyword(s):

Gastric Ulcer ◽

Ulcer Healing ◽

Ellagic Acid ◽

Gastric Ulcer Healing ◽

Cox 2

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

Conservative Dentistry Journal ◽

10.20473/cdj.v11i1.2021.11-18 ◽

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.

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Bakuchiol Suppresses Inflammatory Responses Via the Downregulation of the p38 MAPK/ERK Signaling Pathway

International Journal of Molecular Sciences ◽

10.3390/ijms20143574 ◽

2019 ◽

Vol 20 (14) ◽

pp. 3574 ◽

Cited By ~ 4

Author(s):

Hye-Sun Lim ◽

Yu Jin Kim ◽

Bu-Yeo Kim ◽

Soo-Jin Jeong

Keyword(s):

Mrna Expression ◽

P38 Mapk ◽

Inflammatory Responses ◽

Mitogen Activated Protein Kinase ◽

Enzyme Linked Immunosorbent Assay ◽

Mice Model ◽

Tnf Α ◽

Cox 2

The purpose of the present study was to evaluate the effects of bakuchiol on the inflammatory response and to identify the molecular mechanism of the inflammatory effects in a lipopolysaccharide (LPS)-stimulated BV-2 mouse microglial cell line and mice model. The production of prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) was measured by enzyme-linked immunosorbent assay. The mRNA expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, and IL-6 was measured using reverse transcription–polymerase chain reaction analysis. Mitogen-activated protein kinase (MAPK) phosphorylation was determined by western blot analysis. In vitro experiments, bakuchiol significantly suppressed the production of PGE2 and IL-6 in LPS-stimulated BV-2 cells, without causing cytotoxicity. In parallel, bakuchiol significantly inhibited the LPS-stimulated expression of iNOS, COX-2, and IL-6 in BV-2 cells. However, bakuchiol had no effect on the LPS-stimulated production and mRNA expression of TNF-α or on LPS-stimulated c-Jun NH2-terminal kinase phosphorylation. In contrast, p38 MAPK and extracellular signal-regulated kinase (ERK) phosphorylation were inhibited by bakuchiol. In vivo experiments, Bakuchiol reduced microglial activation in the hippocampus and cortex tissue of LPS-injected mice. Bakuchiol significantly suppressed LPS-injected production of TNF-α and IL-6 in serum. These results indicate that the anti-neuroinflammatory effects of bakuchiol in activated microglia are mainly regulated by the inhibition of the p38 MAPK and ERK pathways. We suggest that bakuchiol may be beneficial for various neuroinflammatory diseases.

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