Expression of polycystins and fibrocystin on primary cilia of lung cells.

Mutations in polycystin-1, polycystin-2, or fibrocystin account for autosomal dominant or recessive polycystic kidney disease. Renal cystogenesis is linked to abnormal localization and function of these cystoproteins in renal primary cilia. They are also expressed in extrarenal tissues in which their functions are unclear.

Chemotherapy drugs form ion pores in membranes due to physical interactions with lipids.

We demonstrate the effects on membrane of the tubulin-binding chemotherapy drugs: thiocolchicoside and taxol. Electrophysiology recordings across lipid membranes in aqueous phases containing drugs were used to investigate the drug effects on membrane conductance. Molecular dynamics simulation of the chemotherapy drug-lipid complexes was used to elucidate the mechanism at an atomistic level.

A protein export pathway involving Escherichia coli porins.

Escherichia coli export the protein YebF into the extracellular medium by a two-step process. However, as no general outer membrane protein secretion system common to all E. coli strains has been reported, the mechanism of export has remained unclear.

Allergic sensitization enhances anion current responsiveness of murine trachea to PAR-2 activation.

Protease-activated receptor 2 (PAR-2) is a G protein-coupled receptor possibly involved in the pathogenesis of asthma. PAR-2 also modulates ion transport in cultured epithelial cells, but these effects in native airways are controversial. The influence of allergic inflammation on PAR-2-induced changes in ion transport has received little attention.

Airway delivery of soluble factors from plastic-adherent bone marrow cells prevents murine asthma.

Asthma affects an estimated 300 million people worldwide and accounts for 1 of 250 deaths and 15 million disability-adjusted life years lost annually. Plastic-adherent bone marrow-derived cell (BMC) administration holds therapeutic promise in regenerative medicine. However, given the low cell engraftment in target organs, including the lung, cell replacement cannot solely account for the reported therapeutic benefits.

The three-dimensional structure of carnocyclin A reveals that many circular bacteriocins share a common structural motif.

Carnocyclin A (CclA) is a potent antimicrobial peptide from Carnobacterium maltaromaticum UAL307 that displays a broad spectrum of activity against numerous Gram-positive organisms. An amide bond links the N and C termini of this bacteriocin, imparting stability and structural integrity to this 60-amino acid peptide. CclA interacts with lipid bilayers in a voltage-dependent manner and forms anion selective pores.

Cholesterol-dependent regulation of adenosine A(2A) receptor-mediated anion secretion in colon epithelial cells.

Cholesterol affects diverse biological processes, in many cases by modulating the function of integral membrane proteins. In this study we have investigated the role of cholesterol in the adenosine-dependent regulation of ion transport in colonic epithelial cells. We observed that methyl-beta-cyclodextrin (MbetaCD), a cholesterol-sequestering molecule, enhanced adenosine A(2A) receptor-activated transepithelial short circuit current (I(sc)), but only from the basolateral side.

The circular bacteriocin, carnocyclin A, forms anion-selective channels in lipid bilayers.

Bacterial resistance to conventional antibiotics is a major challenge in controlling infectious diseases and has necessitated the development of novel approaches in antimicrobial therapy. One such approach is the use of antimicrobial peptides, such as the bacterially produced bacteriocins. Carnocyclin A (CclA) is a 60-amino acid circular bacteriocin produced by Carnobacterium maltaromaticum UAL307 that exhibits potent activity against many Gram-positive bacteria.

Role of calnexin in the ER quality control and productive folding of CFTR; differential effect of calnexin knockout on wild-type and DeltaF508 CFTR.

Cystic fibrosis (CF) is caused by the mutation in CF transmembrane conductance regulator (CFTR), a cAMP-dependent Cl(-) channel at the plasma membrane of epithelium. The most common mutant, DeltaF508 CFTR, has competent Cl(-) channel function, but fails to express at the plasma membrane since it is retained in the endoplasmic reticulum (ER) by the ER quality control system. Here, we show that calnexin (CNX) is not necessary for the ER retention of DeltaF508 CFTR.

Regulation of basolateral Cl(-) channels in airway epithelial cells: the role of nitric oxide.

The presence of basolateral Cl(-) channels in airway epithelium has been reported in several studies, but little is known about their role in the regulation of anion secretion. The purpose of this study was to characterize regulation of these channels by nitric oxide (NO) in Calu-3 cells. Transepithelial measurements revealed that NO donors activated a basolateral Cl(-) conductance sensitive to 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) and anthracene-9-carboxylic acid.

Sodium 4-phenylbutyrate upregulates ENaC and sodium absorption in T84 cells.

Butyrate and other short-chain fatty acids (SCFA), produced by colonic bacterial flora, affect numerous epithelial cell functions. To better understand how SCFA regulate ion transport, we investigated the effects of 4-phenylbutyrate (4-PBA) on Na(+) absorption in T84 cells. Under standard cell culture conditions, the short circuit current did not display any amiloride-sensitive Na(+) absorption and was wholly representative of Cl(-) secretion.

Trichinella spiralis: histamine secretion induced by TSL-1 antigens from unsensitized mast cells.

Mast cells' hyperplasia and activation are prominent features in Trichinella spiralis infection. Recently, it was shown that TSL-1 antigens from T. spiralis muscle larvae induce IL-4 and TNF release by unsensitized, normal mast cells (MC) involving an Ig-independent mechanism.

Differential regulation of cystic fibrosis transmembrane conductance regulator by interferon gamma in mast cells and epithelial cells.

Cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-dependent chloride channel in epithelial cells; recently, we identified it in mast cells. Previous work that we confirmed showed that interferon gamma (IFNgamma) down-regulated CFTR expression in epithelial cells (T84), but by contrast, we found that IFNgamma up-regulated CFTR mRNA and protein expression in rat and human mast cells. IFNgamma up-regulation of CFTR in mast cells was inhibited by p38 and extracellular signal-regulated kinase (ERK) kinase inhibitors but not a Janus tyrosine kinase (JAK)2 inhibitor, whereas in T84 cells IFNgamma-mediated down-regulation of CFTR was JAK2-dependent and ERK- and p38-independent.

Membrane cholesterol content modulates activation of BK channels in colonic epithelia.

Changes in the level of membrane cholesterol regulate a variety of signaling processes including those mediated by acylated signaling molecules that localize to lipid rafts. Recently several types of ion channels have been shown to have cholesterol-dependent activity and to localize to lipid rafts. In this study, we have investigated the role of cholesterol in the regulation of ion transport in colonic epithelial cells.

Syk tyrosine kinase participates in beta1-integrin signaling and inflammatory responses in airway epithelial cells.

The protein tyrosine kinase Syk is critically involved in immunoreceptor signaling in hematopoietic cells. Recent studies demonstrate Syk expression in nonhematopoietic cells, including fibroblasts, endothelial cells, hepatocytes, and breast epithelium. However, the role of Syk in these cells is uncertain.

The role of bestrophin in airway epithelial ion transport.

The purpose of this study was to identify Cl- channels in the basolateral membrane of airway epithelial cells at the molecular level. We have focused on a new family of Cl- channels, bestrophins, which have previously been identified in retinal pigment epithelium. RT-PCR, Western blot and confocal microscopy studies revealed the presence of bestrophin in airway epithelial cells.

The role of the basolateral outwardly rectifying chloride channel in human airway epithelial anion secretion.

The purpose of this study was to characterize basolateral anion channels in Calu-3 and normal human bronchial epithelial cells, and their role in anion secretion. Patch clamp studies identified an outwardly rectifying Cl- channel (ORCC), which could be activated by the adenosine receptor agonist 5'-(N-ethylcarboxamido)adenosine (NECA). Short-circuit current measurements revealed that NECA activates a basolateral, but not an apical, anion conductance sensitive to 4,4'-diisothiocyanatostilbene-2, 2'-disulfonic acid, and to 9-anthracenecarboxylic acid, but not to 4,4'-dinitrostilbene-2,2'-disulfonic acid.

Regulation of Cl- secretion by alpha2-adrenergic receptors in mouse colonic epithelium.

Previous studies have shown that alpha2 adrenoceptor (alpha2AR) agonists inhibit electrolyte secretion in colonic epithelia, but little is known about the molecular mechanisms involved in this process. In this study we examined the effect of alpha2AR activation on transepithelial anion secretion across isolated murine colonic epithelium. We found that alpha2AR agonists, UK 14,304, clonidine and medetomidine were potent inhibitors of anion secretion, especially in the proximal colon.

Nitric oxide activates ATP-dependent K+ channels in human eosinophils.

Nitric oxide (NO) affects the function of ion channels in many cell types, but its role in the regulation of eosinophil ion channels is unknown. In this study, we used the perforated patch-clamp method to investigate the effect of endogenous and exogenous NO on eosinophil ion channels. Using the NO synthase inhibitor, N-nitro-L-arginine methyl ester, we showed that endogenous NO did not affect the whole-cell current in eosinophil.