Oxidized phosphatidylcholines induce multiple functional defects in airway epithelial cells.

Oxidative stress is a hallmark of numerous airway diseases, contributing to extensive cell and tissue damage. Cell membranes and the airway mucosal lining are rich in phospholipids that are particularly susceptible to oxidative attack, producing bioactive molecules including oxidized phosphatidylcholines (OxPCs). With the recent discovery of elevated OxPCs in patients with asthma after allergen challenge, we hypothesized that OxPCs directly contribute to disease by inducing airway epithelial cell dysfunction.

Magnesium sulfate treatment for juvenile ferrets following induction of hydrocephalus with kaolin.

Background: Previous work with 3-week hydrocephalic rats showed that white matter damage could be reduced by the calcium channel antagonist magnesium sulfate (MgSO4). We hypothesized that MgSO4 therapy would improve outcomes in ferrets with hydrocephalus induced with kaolin at 15 days.

Methods: MRI was performed at 29 days to assess ventricle size and stratify ferrets to treatment conditions.

Vitamin D, serum 25(OH)D, LL-37 and polymorphisms in a Canadian First Nation population with endemic tuberculosis.

Background: Canadian First Nation populations have experienced endemic and epidemic tuberculosis (TB) for decades. Vitamin D-mediated induction of the host defence peptide LL-37 is known to enhance control of pathogens such as Mycobacterium tuberculosis.

Objective: Evaluate associations between serum levels of 25-hydroxy vitamin D (25(OH)D) and LL-37, in adult Dene First Nation participants (N = 34) and assess correlations with single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) and vitamin D binding protein (VDBP).

Oral antioxidant therapy for juvenile rats with kaolin-induced hydrocephalus.

Background: Oxidative and nitrosylative changes have been shown to occur in conjunction with the hypoxic changes and cellular/axonal damage in hydrocephalic rodent brains. We hypothesized that antioxidant therapy would improve behavioral, neurophysiological, and/or neurobiochemical outcomes in juvenile rats following induction of hydrocephalus.

Methods: Three-week old rats received an injection of kaolin (aluminum silicate) into the cisterna magna.

Vitamin D in a northern Canadian first nation population: dietary intake, serum concentrations and functional gene polymorphisms.

The wide spectrum of vitamin D activity has focused attention on its potential role in the elevated burden of disease in a northern Canadian First Nations (Dené) cohort. Vitamin D insufficiency, and gene polymorphisms in the vitamin D receptor (VDR) and vitamin D binding protein (VDBP) have been implicated in susceptibility to infectious and chronic diseases. The objectives of this study were to determine the contribution of vitamin D from food, and measure the serum concentrations of 25-hydroxyvitamin D(3) (25-OHD(3)) and VDBP in Dené participants.

Effect of vitamin D supplementation on Mycobacterium tuberculosis-induced innate immune responses in a Canadian Dené First Nations cohort.

Canadian First Nations (FN) population experiences a high burden of tuberculosis. Vitamin D is known to enhance the expression of innate immune effectors, including cathelicidin LL-37, for protection against infections. In this study we performed longitudinal analyses to investigate the impact of vitamin D supplementation on macrophage responses to Mycobacterium tuberculosis (Mtb) lipoprotein (TLR2/1L), in Canadian Dené FN participants compared to Caucasian participants.

Modulation of interleukin-1β-induced inflammatory responses by a synthetic cationic innate defence regulator peptide, IDR-1002, in synovial fibroblasts.

Introduction: Innate defence regulator (IDR) peptides are synthetic cationic peptides, variants of naturally occurring innate immune effector molecules known as host defence peptides. IDR peptides were recently demonstrated to limit infection-associated inflammation selectively without compromising host innate immune functions. This study examined the impact of a 12-amino acid IDR peptide, IDR-1002, in pro-inflammatory cytokine interleukin (IL)-1β-induced responses in synovial fibroblasts, a critical cell type in the pathogenesis of inflammatory arthritis.

Inflammatory cytokines IL-32 and IL-17 have common signaling intermediates despite differential dependence on TNF-receptor 1.

Cytokines IL-32 and IL-17 are emerging as critical players in the pathophysiology of immune-mediated chronic inflammatory diseases. It has been speculated that the molecular mechanisms governing IL-32- and IL-17-mediated cellular responses are differentially dependent on the TNF pathway. In this study, kinome analysis demonstrated that following stimulation with cytokine IL-32, but not IL-17, there was increased phosphorylation of a peptide target corresponding to TNF-R1.