Cigarette smoke alters IL-33 expression and release in airway epithelial cells

AbstractAirway epithelium is a regulator of innate immune responses to a variety of insults including cigarette smoke. Cigarette smoke alters the expression and the activation of Toll Like Receptor 4 (TLR4), an innate immunity receptor. IL-33, an alarmin, increases innate immunity Th2 responses. The aims of this study were to explore whether mini-bronchoalveolar lavage (mini-BAL) or sera from smokers have altered concentrations of IL-33 and whether cigarette smoke extracts (CSE) alter both intracellular expression (mRNA and protein) and release of IL-33 in bronchial epithelial cells. The role of TLR4 in the expression of IL-33 was also explored.Mini-BALs, but not sera, from smokers show red…

Cigarette smoke increases BLT2 receptor functions in bronchial epithelial cells: in vitro and ex vivo evidence

Summary Leukotriene B4 (LTB4) is a neutrophil chemotactic molecule with important involvement in the inflammatory responses of chronic obstructive pulmonary disease (COPD). Airway epithelium is emerging as a regulator of innate immune responses to a variety of insults including cigarette smoke, the major risk factor for COPD. In this study we have explored whether cigarette smoke extracts (CSE) or soluble mediators present in distal lung fluid samples (mini-bronchoalveolar lavages) from smokers alter the expression of the LTB4 receptor 2 (BLT2) and peroxisome proliferator-activated receptor-α (PPAR-α) in bronchial epithelial cells. We also evaluated the effects of CSE on the expression of i…

Immune-Inflammatory Responses and Oxidative Stress in Alzheimers Disease: Therapeutic Implications

Alzheimer's disease (AD) is a heterogeneous and progressive neurodegenerative disease which in Western society mainly accounts for clinical dementia. AD has been linked to inflammation and oxidative stress. Neuro-pathological hallmarks are senile plaques, resulting from the accumulation of several proteins and an inflammatory reaction around deposits of amyloid, a fibrillar protein, Abeta, product of cleavage of a much larger protein, the beta-amyloid precursor protein (APP) and neurofibrillary tangles. Inflammation clearly occurs in pathologically vulnerable regions of AD and several inflammatory factors influencing AD development, i.e. environmental factors (pro-inflammatory phenotype) an…

HLA and killer cell immunoglobulin-like receptors influence the natural course of CMV infection.

Background. Natural killer (NK) cells provide a major defense against cytomegalovirus (CMV) infection through the interaction of their surface receptors, including the activating and inhibitory killer immunoglobulinlike receptors (KIRs), and human leukocyte antigens (HLA) class I molecules. This study assessed whether the KIR and HLA repertoire may influence the risk of developing symptomatic or asymptomatic disease after primary CMV infection in the immunocompetent host. Methods. Sixty immunocompetent patients with primary symptomatic CMV infection were genotyped for KIR and their HLA ligands, along with 60 subjects with a previous asymptomatic infection as controls. Results. The frequency…

Serum and fecal pancreatic enzymes in beta-thalassemia major

This study, using indirect tests, demonstrated that exocrine pancreatic function is impaired in a proportion of patients with beta-thalassemia major (TM), though this impairment is generally mild or moderate.Impaired structure and function of the exocrine pancreas has been reported in patients with Beta-thalassemia major.In this study we measured fecal fats and serum and fecal pancreatic enzymes in 30 patients (13 M, 17 F) with TM, mean age 22.1 yr (range 14-39) and compared them with those of a matched group of healthy controls. Results were correlated with age, serum ferritin, blood transfusion, and various nutritional parameters. Enzymes assays included: serum pancreatic amylase (PA), li…

Efficacy of sublingual immunotherapy with grass allergens for seasonal allergic rhinitis: A systematic review and meta-analysis

Background The benefit of sublingual immunotherapy (SLIT) with grass allergens for seasonal allergic rhinitis has been extensively studied, but data on efficacy are still equivocal. Objective To assess the effectiveness of SLIT with grass allergens in the reduction of symptoms and medication in patients with seasonal allergic rhinitis to grass pollen. Methods Computerized bibliographic searches of MEDLINE (1995-2010) were supplemented by hand searches of reference lists. Studies were included if they were double-blind randomized controlled trials (RCTs) comparing SLIT to placebo and if they included patients with history of allergy to grass pollen treated with natural grass pollen extracts.…

Carbocysteine regulates innate immune responses and senescence processes in cigarette smoke stimulated bronchial epithelial cells

Cigarette smoke represents the major risk factor for chronic obstructive pulmonary disease (COPD). Cigarette smoke extracts (CSE) alter TLR4 expression and activation in bronchial epithelial cells. Carbocysteine, an anti-oxidant and mucolytic agent, is effective in reducing the severity and the rate of exacerbations in COPD patients. The effects of carbocysteine on TLR4 expression and on the TLR4 activation downstream events are largely unknown. This study was aimed to explore whether carbocysteine, in a human bronchial epithelial cell line (16-HBE), counteracted some pro-inflammatory CSE-mediated effects. In particular, TLR4 expression, LPS binding, p21 (a senescence marker), IL-8 mRNA and…

Increased expression of IL-19 in the epithelium of patients with chronic rhinosinusitis and nasal polyps.

Background : Chronic rhinosinusitis (CRS) is an inflammation of the nose and of the paranasal sinuses. The involvement of the respiratory epithelium in the mechanisms of CRS is poorly understood. Aims : Among proteins expressed by nasal epithelial cells in CRS, IL-19 may have key functions. We here aimed to determine the expression and regulation of IL-19. Methods : Nasal biopsies from normal subjects (n = 12), subjects with CRS but without nasal polyps (NP) (CRSsNP, n = 12) and with CRS with NP (CRSwNP, n = 15) were collected. Human Asthma Gene Array and real-time PCR were used to evaluate gene expression, western blot analysis and immunohistochemistry for protein expression. Results for I…

Identification of inflammatory molecules with an important role in the pathogenesis of the Chronic Rhinosinuitis.

Pleural Mesothelial Cells Express Both BLT2 and PPARα and Mount an Integrated Response to Pleural Leukotriene B4

Abstract Leukotriene B4 (LTB4) plays a crucial role in the recruitment of neutrophils into the pleural space. We identified for the first time the mechanisms by which LTB4 interacts with mesothelial cells and recruits neutrophils in the pleural compartment. Primary pleural mesothelial cells express both the proinflammatory receptor for LTB4 BLT2, and the anti-inflammatory receptor for LTB4, PPARα. Parapneumonic pleural effusions highly increase BLT2 expression and, via BLT2 activation, increase the adhesion between mesothelial cells and neutrophils and the expression of ICAM-1 on mesothelial cells. The block of PPARα further increases both cell adhesion and ICAM-1 expression. BLT2 activatio…