scholarly journals Roles of Thromboxane Receptor Signaling in Enhancement of Lipopolysaccharide-Induced Lymphangiogenesis and Lymphatic Drainage Function in Diaphragm

2021 ◽  
Author(s):  
Hiromi Matsuda ◽  
Yoshiya Ito ◽  
Kanako Hosono ◽  
Seri Tsuru ◽  
Tomoyoshi Inoue ◽  
...  
Keyword(s):  
T Cells ◽  
Arachidonic Acid ◽  
Lymphatic Drainage ◽  
Arachidonic Acid Metabolite ◽  
Dependent Manner ◽  
Wild Type ◽  
Acid Metabolite ◽  
Thromboxane Receptor ◽  
Novel Target ◽  
Factor C

Objective: Thromboxane is an arachidonic acid metabolite that exerts its actions through a G-protein–coupled receptor with 7 transmembrane domains. Although an arachidonic acid metabolite, prostaglandin E2 was reported to enhance lymphangiogenesis, little is known on other arachidonic acid metabolites. In the present study, we investigated the roles of TP (thromboxane prostanoid) signaling in facilitating lymphangiogenesis during inflammation. Approach and Results: Inflammation was induced by repeated intraperitoneal injections of lipopolysaccharide, and lymphangiogenesis essential for draining peritoneal fluids was estimated in the diaphragm. Lipopolysaccharide induced lymphangiogenesis in the diaphragm in a time-dependent manner in wild-type mice. Compared with wild-type mice, lipopolysaccharide-induced lymphangiogenesis in TP-deficient (TP −/− ) mouse diaphragm tissues was suppressed, and this was accompanied by reduced drainage function from the peritoneal cavity. TP-positive macrophages and T cells were accumulated in the diaphragm and produced VEGF (vascular endothelial growth factor)-C and VEGF-D in a TP-dependent manner. Removal of macrophages and T cells resulted in reduced lymphangiogenesis and lowered expressions of VEGF-C and VEGF-D. Furthermore, TP −/− bone marrow chimeric mice exhibited reduced lymphangiogenesis. TP knockout specific to macrophages and T cells also led to reduced lymphangiogenesis and drainage function in mice with lipopolysaccharide injections. Conclusions: The present results suggest that TP signaling exerts prolymphangiogenic activity by acting on macrophages and T cells accumulated during inflammation and that TP signaling represents a novel target for controlling lymphangiogenesis.

scholarly journals Arachidonic Acid Metabolite 19(S)-HETE Induces Vasorelaxation and Platelet Inhibition by Activating Prostacyclin (IP) Receptor

PLoS ONE ◽  
2016 ◽  
Vol 11 (9) ◽  
pp. e0163633 ◽  
Author(s):  
Sorin Tunaru ◽  
Ramesh Chennupati ◽  
Rolf M. Nüsing ◽  
Stefan Offermanns
Keyword(s):  
Arachidonic Acid ◽  
Platelet Inhibition ◽  
Arachidonic Acid Metabolite ◽  
Acid Metabolite ◽  
Ip Receptor

scholarly journals Mediation of Arachidonic Acid Metabolite(s) Produced by Endothelial Cytochrome P-450 3A4 in Monkey Arterial Relaxation.

2003 ◽  
Vol 26 (3) ◽  
pp. 237-243 ◽  
Author(s):  
Kazuhide AYAJIKI ◽  
Hideyuki FUJIOKA ◽  
Noboru TODA ◽  
Shigeru OKADA ◽  
Yukiko MINAMIYAMA ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Arachidonic Acid Metabolite ◽  
Acid Metabolite ◽  
Arterial Relaxation ◽  
Cytochrome P 450

scholarly journals The G0/G1 switch gene 2 is a novel PPAR target gene

2005 ◽  
Vol 392 (2) ◽  
pp. 313-324 ◽  
Author(s):  
Fokko Zandbergen ◽  
Stéphane Mandard ◽  
Pascal Escher ◽  
Nguan Soon Tan ◽  
David Patsouris ◽  
...  
Keyword(s):  
Chromatin Immunoprecipitation ◽  
Target Gene ◽  
Mrna Level ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Wild Type ◽  
Hepatic Expression ◽  
Peroxisome Proliferator Activated Receptors ◽  
Novel Target ◽  
Responsive Element

PPARs (peroxisome-proliferator-activated receptors) α, β/δ and γ are a group of transcription factors that are involved in numerous processes, including lipid metabolism and adipogenesis. By comparing liver mRNAs of wild-type and PPARα-null mice using microarrays, a novel putative target gene of PPARα, G0S2 (G0/G1 switch gene 2), was identified. Hepatic expression of G0S2 was up-regulated by fasting and by the PPARα agonist Wy14643 in a PPARα-dependent manner. Surprisingly, the G0S2 mRNA level was highest in brown and white adipose tissue and was greatly up-regulated during mouse 3T3-L1 and human SGBS (Simpson–Golabi–Behmel syndrome) adipogenesis. Transactivation, gel shift and chromatin immunoprecipitation assays indicated that G0S2 is a direct PPARγ and probable PPARα target gene with a functional PPRE (PPAR-responsive element) in its promoter. Up-regulation of G0S2 mRNA seemed to be specific for adipogenesis, and was not observed during osteogenesis or myogenesis. In 3T3-L1 fibroblasts, expression of G0S2 was associated with growth arrest, which is required for 3T3-L1 adipogenesis. Together, these data indicate that G0S2 is a novel target gene of PPARs that may be involved in adipocyte differentiation.

scholarly journals Role of superoxide and thromboxane receptors in acute angiotensin II-induced vasoconstriction of rabbit vessels

2011 ◽  
Vol 300 (6) ◽  
pp. H2064-H2071 ◽  
Author(s):  
Sandra L. Pfister ◽  
Kasem Nithipatikom ◽  
William B. Campbell
Keyword(s):  
Arachidonic Acid ◽  
Angiotensin Ii ◽  
Rabbit Aorta ◽  
Arachidonic Acid Metabolite ◽  
Maximal Contraction ◽  
Nitric Oxide Synthase Inhibitor ◽  
Thromboxane Receptor ◽  
Thromboxane Receptors ◽  
Thromboxane Receptor Antagonist ◽  
Synthase Inhibitor

This study explored the hypothesis that a portion of angiotensin II-induced contractions is dependent on superoxide generation and release of a previously unidentified arachidonic acid metabolite that activates vascular smooth muscle thromboxane receptors. Treatment of rabbit aorta or mesentery artery with the thromboxane receptor antagonist SQ29548 (10 μM) reduced angiotensin II-induced contractions (maximal contraction in aorta; control vs. SQ29548: 134 ± 16 vs. 93 ± 10%). A subset of rabbits deficient in vascular thromboxane receptors also displayed decreased contractions to angiotensin II. The superoxide dismutase mimetic Tiron (30 mM) attenuated angiotensin II-induced contractions only in rabbits with functional vascular thromboxane receptors (maximal contraction in aorta; control vs. Tiron: 105 ± 5 vs. 69 ± 11%). Removal of the endothelium or treatment with a nitric oxide synthase inhibitor, nitro-l-arginine (30 μM) did not alter angiotensin II-induced contractions. Tiron and SQ29548 decreased angiotensin II-induced contractions in the denuded aortas by a similar percentage as that observed in intact vessels. The cyclooxygenase inhibitor indomethacin (10 μM) or thromboxane synthase inhibitor dazoxiben (10 μM) had no effect on angiotensin II-induced contractions indicating that the vasoconstrictor was not thromboxane. Angiotensin II increased the formation of a 15-series isoprostane. Isoprostanes are free radical-derived products of arachidonic acid. The unidentified isoprostane increased when vessels were incubated with the superoxide-generating system xanthine/xanthine oxidase. Pretreatment of rabbit aorta with the isoprostane isolated from aortic incubations enhanced angiotensin II-induced contractions. Results suggest the factor activating thromboxane receptors and contributing to angiotensin II vasoconstriction involves the superoxide-mediated generation of a 15-series isoprostane.

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