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Wnt5a is a ligand that activates the noncanonical Wnt signaling pathways (b-catenin-independent pathways). Human neutrophils expressed several Wnt5a receptors, such as Frizzled 2, 5 and 8. Stimulation of human neutrophils with Wnt5a caused chemotactic migration and the production of two important chemokines, CXCL8 and CCL2. CCL2 production by Wnt5a was mediated by a pertussis toxin-sensitive G-protein-dependent pathway. Wnt5a also stimulated the phosphorylation of three mitogen-activated protein

In this study, we examined the therapeutic effects of an immune-stimulating peptide, WKYMVm, in ulcerative colitis. The administration of WKYMVm to dextran sodium sulfate (DSS)-treated mice reversed decreases in body weight, bleeding score and stool score in addition to reversing DSS-induced mucosa destruction and shortened colon. The WKYMVm-induced therapeutic effect against ulcerative colitis was strongly inhibited by a formyl peptide receptor (FPR) 2 antagonist, WRWWWW,indicating the crucial

Serum amyloid A (SAA) induced CCL2 production via a pertussis toxin (PTX)-insensitive pathway in human umbilical vein endothelial cells (HUVECs). SAA induced the activation of three MAPKs (ERK, p38 MAPK,and JNK), which were completely inhibited by knock-down of formyl peptide receptor 2 (FPR2). Inhibition of p38 MAPK and JNK by their specific inhibitors (SB203580 and SP600125), or inhibition by a dominant negative mutant of p38 MAPK dramatically decreased SAA-induced CCL2 production. Inactivatio

Neutrophils play a key role in innate immunity, and the identification of new stimuli that stimulate neutrophil activity is a very important issue. In this study, we identified three novel peptides by screening a synthetic hexapeptide combinatorial library. The identified peptides GMMWAI, MMHWAM, and MMHWFM caused an increase in intracellular Ca2+ in a concentration-dependent manner via phospholipase C activity in human neutrophils. The three peptides acted specifically on neutrophils and monocy

Neutrophils play an important role in the initiation of innateimmunity against infection and injury. Although manydifferent types of G-protein coupled receptors are functionallyexpressed in neutrophils, no reports have demonstratedfunctional expression of umami taste receptor in these cells. We observed that mouse neutrophils express the umami tastereceptor T1R1/T1R3 through RNA sequencing and quantitativeRT-PCR analysis. Stimulation of mouse neutrophils withL-alanine or L-serine, which are liga

When mouse bone marrow-derived macrophages were stimulated with serum amyloid A (SAA), which is a major acute-phase protein, there was strong inhibition of osteoclast formation induced by the receptor activator of nuclear factor kappaB ligand. SAA not only markedly blocked the expression of several osteoclast-associated genes (TNF receptor-associated factor 6 and osteoclast-associated receptor) but also strongly induced the expression of negative regulators (MafB and interferon regulatory factor

We investigated the effect of lysophosphatidic acid (LPA) in experimental acetaminophen (APAP)-induced acute liver injury. LPA administration significantly reduced APAP-challenged acute liver injury, showing attenuated liver damage, liver cell death and aspartate aminotransferase and alanine aminotransferase levels. APAP overdose-induced mortality was also significantly decreased by LPA administration. Regarding the mechanism involved in LPA-induced protection against acute liver injury, LPA adm

In this study, we report that one of the antimicrobial peptides scolopendrasin VII, derived from Scolopendra subspinipes mutilans, stimulates actin polymerization and the subsequent chemotactic migration of macrophages through the activation of ERK and protein kinase B (Akt) activity. The scolopendrasin VII-induced chemotactic migration of macrophages is inhibited by the formyl peptide receptor 1 (FPR1) antagonist cyclosporine H. We also found that scolopendrasin VII stimulate the chemotactic mi

Sepsis is a life-threatening, infectious, systemic inflammatory disease. In this study, we investigated the therapeutic effect of α-cubebenoate, a novel compound isolated from Schisandra chinensis against polymicrobial sepsis in a cecal ligation and puncture (CLP) experimental model. Administration of α-cubebenoate strongly enhanced survival in the CLP model. α-cubebenoate administration also markedly blocked CLP-induced lung inflammation and increased bactericidal activity by enhancing phagocyt

In this study, we report that an acute phase reactant, serum amyloid A (SAA), strongly inhibits dendritic cell differentiation induced by GM-CSF plus IL-4. SAA markedly decreased the expression of MHCII and CD11c. Moreover, SAA decreased cell surface GM-CSF receptor expression. SAA also decreased the expression of PU.1 and C/EBPα, which play roles in the expression of GM-CSF receptor. This inhibitory response by SAA is partly mediated by the well-known SAA receptors, Toll-like receptor 2 and for

We investigated the effects of two antimicrobial peptides (AMPs) isolated from Scolopendra subspinipes mutilans on neutrophil activity. Stimulation of mouse neutrophils with the two AMPs elicited chemotactic migration of the cells in a pertussis toxin-sensitive manner. The two AMPs also stimulated activation of ERK and Akt, which contribute to chemotactic migration of neutrophils. We found that AMP-stimulated neutrophil chemotaxis was blocked by a formyl peptide receptor (FPR) 1 antagonist (cycl

This study investigated the effects of (10Z)-1-[(5Z,8Z)-tetradeca-5,8-dienoyloxy]-3-[(Z)-tetradec-8-enoyloxy]propan-2-yl hexadec-10-enoate (TTPH) from garlic on the inducible nitric oxide synthase (iNOS) and cycloxygenase-2 (COX-2)systems in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The TTPH dose-dependently reduced nitriteaccumulation and production of prostaglandin E2 in the supernatants of LPS-stimulated macrophages. Markedly reducediNOS and COX-2 enzyme activities were observ

Formyl peptide receptors (FPRs) belong to the G protein-coupled receptor (GPCR) family and are well known as chemotactic receptors and pattern recognition receptors (PRRs) that recognize bacterial and mitochondria-derived formylated peptides. FPRs are also known to detect a wide range of ligands, including host-derived peptides and lipids. FPRs are highly expressed not only in phagocytes such as neutrophils, monocytes, and macrophages but also in nonhematopoietic cells such as epithelial cells a

Garlic has garnered attention as a useful material which contains many bioactive molecules for the prevention and/or treatment of various human ailments, including infectious diseases. In this study we tested several extracts of garlic on cellular activity in human neutrophils. Stimulation of human neutrophils with chloroform extract of garlic (GCE) elicited intracellular calcium ([Ca2+]i) increases in a phospholipase C independent manner. GCE also stimulated superoxide anion production, which w

Pseudomonas aeruginosa (P. aeruginosa) is a well-known Gramnegativeopportunistic pathogen. Neutrophils play key roles inmediating host defense against P. aeruginosa infection. In thisstudy, we identified a metabolite derived from P. aeruginosa thatregulates neutrophil activities. Using gas chromatography-massspectrometry, a markedly increased level of 2-undecanone wasidentified in the peritoneal fluid of P. aeruginosa-infected mice. 2-Undecanone elicited the activation of neutrophils in a Gαi-ph