Pleurocidins are a novel family of α-helical cationic antimicrobial peptides (CAPs) that are structurally and functionally similar to cathelicidins, one of the major CAP families. As cathelicidins stimulate mast cell chemotaxis and mediator release, we postulated that pleurocidins similarly activate mast cells. A screen of 20 pleurocidin peptides revealed that some were capable of degranulating the human mast cell line LAD2 (Laboratory of Allergic Diseases 2). Pleurocidin NRC-04 caused LAD2 to adhere, migrate, degranulate, and release cysteinyl leukotrienes and prostaglandin D2. Moreover, pleurocidin increased intracellular Ca(2+) mobilization in mast cells and induced the production of proinflammatory chemokines such as monocyte chemotactic protein-1/C-C motif chemokine ligand 2 (CCL2) and macrophage inflammatory protein-1β/CCL4. Our evaluation of possible cellular mechanisms suggested that G proteins, phosphoinositol-3 kinase (PI3K), phospholipase C (PLC), and phosphokinase C (PKC) were involved in pleurocidin-induced mast cell activation as evidenced by the inhibitory effects of pertussis toxin (G protein inhibitor), wortmanin (PI3K inhibitor), U-73122 (PLC inhibitor), and Ro-31-8220 (PKC inhibitor), respectively. We also found that human mast cells expressed the N-formyl-peptide receptor 1 (FPRL1) receptor and FPRL1-specific inhibitor affected pleurocidin-mediated activation of mast cell. Our finding that the novel CAP pleurocidin activated human mast cell through G protein-coupled receptor signaling suggests that this peptide might have immunomodulatory functions.

Catalli, Adriana, and Luke J. Janssen. Augmentation of bovine airway smooth muscle responsiveness to carbachol, KCl, and histamine by the isoprostane 8-iso-PGE 2. Am J Physiol Lung Cell Mol Physiol 287: L1035-L1041, 2004. First published July 16, 2004 doi:10.1152/ajplung.00138.2004Isoprostanes are generated during periods of oxidative stress, which characterize diseases such as asthma and cystic fibrosis. They also elicit functional responses and may therefore contribute to the pathology of these diseases. We set out to examine the effects of isoprostanes on airway responsiveness to cholinergic stimulation. Muscle bath techniques were employed using isolated bovine tracheal smooth muscle. 8-Isoprostaglandin E 2 (8-iso-PGE 2) increased tone directly on its own, although the magnitude of this response, even at the highest concentration tested, was only a fraction of that evoked by KCl or carbachol. More importantly, though, pretreatment of the tissues with 8-iso-PGE 2 (10 M) markedly augmented responses to submaximal and even subthreshold concentrations of KCl, carbachol, or histamine, whereas maximal responses to these agents were unaffected by the isoprostane. The augmentative effect on cholinergic responsiveness was mimicked by PGE 2 (0.1 M) and by the FP agonists PGF2 (0.1 M) and fluprostenol (0.1 M), but not by the EP3 agonist sulprostone (0.1 M) or the TP agonist U-46619 (0.1 M). Antagonists of EP1 receptors (AH-6809 and SC-19920, 10 M) and TP receptors (ICI-192605, 1 M) had no effect on 8-iso-PGE2-induced augmentation of cholinergic responsiveness. We conclude that 8-iso-PGE2 induces nonspecific airway smooth muscle hyperresponsiveness through a non-TP non-EP prostanoid receptor. prostanoid receptors; contraction; asthma; oxidative stress; 8-isoprostaglandin E2 ISOPROSTANES ARE A LARGE GROUP of free radical-generated, prostaglandin-like molecules that have proven useful as markers of oxidative stress. Only recently have researchers begun to recognize these molecules as having their own potent biological activity. Most research to date has focused solely on the excitatory actions of isoprostane 8-iso-PGF 2␣ , which is responsible for such physiological responses as vasoconstriction, bronchoconstriction (22,25,27), and modulation of platelet aggregation (28,38).Isoprostanes are detected in normal human plasma, urine, bronchoalveolar lavage fluid (33-35), and exhaled breath condensates (31). More importantly, their concentrations are significantly elevated during periods of oxidative stress, which characterizes such diseases as asthma (2,3,31,45), chronic obstructive pulmonary disorder (30, 37), interstitial lung disease (29), and cystic fibrosis (9,11,32) and as such may contribute to the pathology underlying these conditions.There are a number of reports indicating that isoprostanes exert their biological effects through classic prostanoid receptors. This is not surprising considering the strong structural similarities between isoprostanes and prostaglandins; both groups of molecules possess a cyclopentane ...

The effect of the neuropeptide substance P (SP) on human mast cell (MC) phenotype is poorly understood. In this study, SP effects on human MC expression of the high affinity IgE receptor (FcεRI) were characterized. SP downregulated expression of FcεRI mRNA and protein by approximately 50% and in a concentration dependent manner, the effect was partially mediated by engagement of the neurokinin-1 receptor (NK1R) and resulted in reduced mast cell activation. Sensitization of MC with IgE prior to SP exposure protected MC from SP-mediated FcεRI downregulation. SP release may inhibit MC responses to allergens and these results may have implications in neuroinflammatiion and stress.

Prostate cancer is one of the most common cancers in the world, and its prevalence is expected to increase appreciably in the coming decades. As such, more research is necessary to understand the etiology, progression and possible preventative measures to delay or to stop the development of this disease. Recently, there has been interest in examining the effects of whole extracts from commonly harvested crops on the behaviour and progression of cancer. Here, we describe the effects of whole cranberry extract (WCE) on the behaviour of DU145 human prostate cancer cells in vitro. Following treatment of DU145 human prostate cancer cells with 10, 25 and 50 μg ml⁻¹ of WCE, respectively for 6 h, WCE significantly decreased the cellular viability of DU145 cells. WCE also decreased the proportion of cells in the G2-M phase of the cell cycle and increased the proportion of cells in the G1 phase of the cell cycle following treatment of cells with 25 and 50 μg ml⁻¹ treatment of WCE for 6 h. These alterations in cell cycle were associated with changes in cell cycle regulatory proteins and other cell cycle associated proteins. WCE decreased the expression of CDK4, cyclin A, cyclin B1, cyclin D1 and cyclin E, and increased the expression of p27. Changes in p16(INK4a) and pRBp107 protein expression levels also were evident, however, the changes noted in p16(INK4a) and pRBp107 protein expression levels were not statistically significant. These findings demonstrate that phytochemical extracts from the American cranberry (Vaccinium macrocarpon) can affect the behaviour of human prostate cancer cells in vitro and further support the potential health benefits associated with cranberries.

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