T Cell Activation Depends on Extracellular Alanine.

T cell stimulation is metabolically demanding. To exit quiescence, T cells rely on environmental nutrients, including glucose and the amino acids glutamine, leucine, serine, and arginine. The expression of transporters for these nutrients is tightly regulated and required for T cell activation.

Hematopoietic prostaglandin D synthase-derived prostaglandin D ameliorates adjuvant-induced joint inflammation in mice.

Although prostaglandins (PGs) are known to be involved in the progression of arthritis, the role of PGD remains unclear. In this study, we evaluated the role of PGD in joint inflammation using genetically modified mice. Injection of complete Freund's adjuvant (CFA) increased the production of PGD and induced paw swelling and cartilage erosion in wild-type (WT) mice.

VEGF-induced blood flow increase causes vascular hyper-permeability in vivo.

VEGF is known to cause vascular leak, its detailed mechanisms in vivo remain unclear. Here, we investigated the mechanisms underlying VEGF-induced vascular hyper-permeability focusing on two major regulators of vascular permeability: blood flow and endothelial barrier function. Administration of VEGF caused vascular hyper-permeability and tissue swelling in mouse ears, which were abolished by VEGF receptor-2 blockade.

Histamine Induces Vascular Hyperpermeability by Increasing Blood Flow and Endothelial Barrier Disruption In Vivo.

Histamine is a mediator of allergic inflammation released mainly from mast cells. Although histamine strongly increases vascular permeability, its precise mechanism under in vivo situation remains unknown. We here attempted to reveal how histamine induces vascular hyperpermeability focusing on the key regulators of vascular permeability, blood flow and endothelial barrier.

A deficiency in the prostaglandin D2 receptor CRTH2 exacerbates adjuvant-induced joint inflammation.

Although the cyclooxygenase metabolites PGs are known to be involved in the progression of arthritis, the role of PGD2 remains unclear. In this study, we evaluated the contribution of signaling mediated through a PGD2 receptor, chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2), in the progression of adjuvant-induced joint inflammation. Injection of CFA into the ankle joint stimulated PGD2 production and induced paw swelling in both CRTH2-naive (WT) and CRTH2(-/-) mice.

Opposing immunomodulatory roles of prostaglandin D2 during the progression of skin inflammation.

The effects of PGD2 are extremely context dependent. It can have pro- or anti-inflammatory effects in clinically important pathological conditions. A greater mechanistic insight into the determinants of PGD2 activity during inflammation is thus required.

Bile acid receptor TGR5 agonism induces NO production and reduces monocyte adhesion in vascular endothelial cells.

Objective: TGR5 is a G-protein-coupled receptor for bile acids. So far, little is known about the function of TGR5 in vascular endothelial cells.

Approach And Results: In bovine aortic endothelial cells, treatment with a bile acid having a high affinity to TGR5, taurolithocholic acid (TLCA), significantly increased NO production.

Anti-inflammatory role of PGD2 in acute lung inflammation and therapeutic application of its signal enhancement.

We investigated the role of prostaglandin D2 (PGD2) signaling in acute lung injury (ALI), focusing on its producer-effector interaction in vivo. Administration of endotoxin increased edema and neutrophil infiltration in the WT mouse lung. Gene disruption of hematopoietic PGD synthase (H-PGDS) aggravated all of the symptoms.

Prostaglandin D2-DP signaling promotes endothelial barrier function via the cAMP/PKA/Tiam1/Rac1 pathway.

Objective: Prostaglandin D(2) (PGD(2)) is one of the prostanoids produced during inflammation. Although PGD(2) is known to decrease endothelial permeability through D prostanoid (DP) receptor stimulation, the detailed mechanism is unknown.

Methods And Results: Treatment with PGD(2) (0.

γ-Oryzanol reduces adhesion molecule expression in vascular endothelial cells via suppression of nuclear factor-κB activation.

γ-Oryzanol (γ-ORZ) is a mixture of phytosteryl ferulates purified from rice bran oil. In this study, we examined whether γ-ORZ represents a suppressive effect on the lipopolysaccharide (LPS)-induced adhesion molecule expression on vascular endothelium. Treatment with LPS elevated the mRNA expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin in bovine aortic endothelial cells (BAECs).

Halichlorine reduces monocyte adhesion to endothelium through the suppression of nuclear factor-kappaB activation.

Halichlorine is a marine alkaloid isolated from the marine sponge Halichondria okadai KADOTA, and its pathophysiological effect on vascular cells remains unknown. Here, we examined the anti-atherosclerosis activity of halichlorine on endothelial cells by assessing the expression of adhesion molecules. In bovine aortic endothelial cells (BAECs), pretreatment with halichlorine (10 microM, 2 h) inhibited lipopolysaccharide (LPS) (3 microg/ml, 3 h)-induced mRNA expressions of vascular cell adhesion molecule (VCAM-1), intercellular adhesion molecule (ICAM-1), and E-selectin.

Halichlorine is a novel L-type Ca(2+) channel inhibitor isolated from the marine sponge Halichondria okadai Kadota.

Halichlorine, isolated from a marine sponge Halichondria okadai Kadota, has a unique structure and its physiological activity is virtually unknown. In the present study, we investigated the direct effect of halichlorine on vascular contractility. In endothelium-denuded rat aorta, while the treatment of halichlorine (0.