Inflammation & Allergy-Drug Targets (v.11, #6)
Editorial (Progress and Prospects in Scientific Publications ? A Call for More Transparency and Less Voluminous Output) by Kurt S. Zaenker (421-421).
Pentoxifylline Use in Dermatology by Seray Kulcu Cakmak, Atil Cakmak, Muzeyyen Gonul, Arzu Kilic, Ulker Gul (422-432).
Pentoxifylline is methylxanthine derivative which is used in microcirculatory disorders as a vasoactive drug. Novel immunomodulatory properties of pentoxifylline have been reported including the down regulation of tumour necrosis factor-α synthesis and other inflammatory cytokines. Studies have shown that pentoxifylline might be efficacious in a wide spectrum of skin diseases. This article focuses on the use of pentoxifylline which is a safe and cheap drug in various dermatological disorders.
Neutrophil Activation Induced by Plant Lectins: Modulation of Inflammatory Processes by Gabriela Pereira-da-Silva, Fernanda Caroline Carvalho, Maria Cristina Roque-Barreira (433-441).
Lectins are ubiquitous proteins that exhibit selective and reversible carbohydrate-binding activities, and have become increasingly known as cell recognition mediators in a wide range of biological systems. Besides being useful tools in the study of underlying mechanisms involved in inflammation, lectins have also emerged as suitable molecules for pharmaceutical applications. Since the discovery that mammalian lectins exert crucial roles in neutrophil adhesion, mobilization, and activation, the experimental use of lectins from exogenous sources, such as plants, as modulators of leukocyte functions has been considered. Indeed, specific mammalian cell responses triggered by different plant lectins have contributed to delineation of the signaling mechanisms underlying cell adhesion, intracellular activation, and modulation of cell responses. This review presents a comprehensive summary of research concerning the effects of plant lectins on the main physiological activities of neutrophils, such as migration, degranulation, release of inflammatory mediators, phagocytosis, and apoptosis. The reports included herein illustrate the modulation of inflammatory processes by plant lectins.
Cardiac Remodeling Induced by Smoking: Concepts, Relevance, and Potential Mechanisms by Marcos F. Minicucci, Paula S. Azevedo, Bertha F. Polegato, Sergio A.R. Paiva, Leonardo A.M. Zornoff (442-447).
Cardiac or ventricular remodeling is characterized by molecular, cellular, and interstitial alterations that lead to changes in heart size, mass, geometry and function in response to a given insult. Currently, tobacco smoke exposure is recognized as one of these insults. Indeed, tobacco smoke exposure induces the enlargement of the left-sided cardiac chambers, myocardial hypertrophy, and ventricular dysfunction. Potential mechanisms for these alterations include hemodynamic and neurohormonal changes, oxidative stress, inflammation, nitric oxide bioavailability, matrix metalloproteinases and mitogen-activated protein kinase activation. This review will focus on the concepts, relevance, and potential mechanisms of cardiac remodeling induced by tobacco smoke.
New Insights into HLA-G and Inflammatory Diseases by Roberta Rizzo, Daria Bortolotti, Olavio R. Baricordi, Enrico Fainardi (448-463).
Human leucocyte antigen-G (HLA-G) is a non-classical HLA class I molecule with an important role at the fetus-maternal interface, preventing fetus recognition and abortion. The role of HLA-G as an immune-modulatory and anti-inflammatory molecule has led to investigate its role in pathological conditions. In these years, HLA-G has been shown to have an important implication in inflammatory pathologies. The focus of this review is to up-date the scientific knowledge on the expression of HLA-G molecules in inflammatory conditions.
Toll-Like Receptors and their Role in Renal Pathologies by Theodoros Eleftheriadis, Georgios Pissas, Vassilios Liakopoulos, Ioannis Stefanidis, Brian R. Lawson (464-477).
Toll-like receptors (TLRs) are the first identified and best studied family of pattern recognition receptors. Expressed in immunocytes, TLRs initiate innate immune responses and concurrently shape the subsequent adaptive immune response. They are sensors of both pathogens, through the exogenous pathogen-associated molecular patterns (PAMPs), and tissue injury, through the endogenous danger-associated molecular patterns (DAMPs). In addition to immunocytes, TLRs are widely distributed in various cell types, including renal cells where they contribute significantly to various pathologies. In particular, many experimental and emerging clinical data indicate that TLRs are involved in the pathogenesis of urinary tract infections, sepsis-induced renal failure, kidney ischemia/reperfusion injury, idiopathic or systemic autoimmunity-induced glomerulonephritis and ultimately is renal fibrosis, which leads to end-stage renal disease. This review summarizes the present data about the important role TLRs play in the above kidney diseases focusing on the specific role of PAMPs versus DAMPs and of local versus systemic TLR activation.
Innate Immunity in the Pathogenesis of Cholangiopathy: A Recent Update by Kenichi Harada, Yasuni Nakanuma (478-483).
Biliary innate immunity is involved in the pathogenesis of cholangiopathies in patients with various biliary diseases. Biliary epithelial cells possess an innate immune system consisting of the Toll-like receptor (TLR) family and recognize pathogen-associated molecular patterns (PAMPs). Recently, regulatory mechanisms by intracellular negative regulators including peroxisome proliferator-activated receptor-γ and micro-RNA have been clarified. In primary biliary cirrhosis (PBC) and primary sclerosing cholangitis, dysregulated biliary innate immunity, namely hyper-responsiveness to PAMPs, is associated with the histopathogenesis of cholangiopathy. Moreover, biliary epithelial cells produce monocyte chemotactic protein-1 (MCP-1/CCL2) as a result of the innate immune response and bile ductules play a role in hepatic fibrosis caused by hepatic stellate cells (HSCs). Also, biliary innate immune responses induce the production of two chemokines, fractalkine and macrophage inflammatory protein-3α (MIP-3α), causing the migration of inflammatory cells and a population of antigen-presenting cell found in epithelium, Langerhans cell, and involve chronic cholangitis associated with biliary epithelium-specific innate and acquired immunity in PBC.
The Therapeutic Potential of Toll-Like Receptor 7 Stimulation in Asthma by Matthew G. Drake, Elad H. Kaufman, Allison D. Fryer, David B. Jacoby (484-491).
Asthma is an inflammatory disorder of the airways frequently characterized by an excessive Th2 adaptive immune response. Activation of Toll-like receptor (TLR)-7, a single-stranded viral RNA receptor that is highly expressed in the airways, triggers a rapid innate immune response and favors a subsequent Th1 response. Because of this role in pulmonary immunoregulation, TLR7 has gained considerable interest as a therapeutic target in asthma. Synthetic TLR7 ligands, including the imidazoquinolines imiquimod (R837) and resiquimod (R848), and 8-hydroxyadenine derivatives have been developed for other clinical indications. TLR7 activation prevents ovalbumin-induced airway hyperreactivity, eosinophilic inflammation, goblet cell hyperplasia and airway remodeling in murine models of asthma. TLR7 activation also inhibits viral replication in the lung and prevents virus-induced airway hyperreactivity. Furthermore, it has recently been shown that stimulating TLR7 rapidly relaxes airway smooth muscle, dilating the airways. This bronchodilating effect, which occurs in seconds to minutes and depends on rapid production of nitric oxide, indicates that TLR7 can signal via previously unrecognized pathways. The effects of decreasing the allergic Th2 response, acting as an immediate bronchodilator, and promoting an antiviral immune environment, make TLR7 an attractive drug target. We examine the current understanding of TLR7 as a therapeutic target and its translation to asthma treatment in humans.
Diabetogenic Effects of Parthinium hysterophorous Induced Allergic Rhinitis by Vinita Tiwari, Hamendra Singh Parmar (492-498).
Diabetes mellitus (DM) is known to be associated with the cytokines secreted by Th1 cells, while allergic rhinitis (AR) is mainly regulated by Th2 cytokines. According to Th1/Th2 paradigm, there is an inverse relationship between Th1 and Th2 cytokines and resultantly, both the aforesaid diseases are also inversely correlated. On the other hand, numbers of clinical reports suggest every possible correlation between DM and AR including positive, negative and neutral. However, till to date, no experimental report available, suggesting the changes in glucose homeostasis of animal model(s) of allergic rhinitis, if any. Therefore, in the present study we have observed the changes in glucose homeostasis of the animals bearing AR induced by Parthinium hysterophorous (PH). The condition of AR was induced by intranasal instillations of the acetone extract of PH. At the end of experimentation, various parameters for AR and DM were evaluated. A significant increase was observed in total leukocytes in nasal fluid, serum glucose, thyroxine, dyslipidemia and activity of α-amylase, pancreatic lipid peroxidation, serum and pancreatic nitrite with a concomitant reduction in serum calcium, triiodothyronine, hepatic glycogen and activity of phosphoglucomutase. However, serum insulin, TSH, pancreatic calcium and hepatic glucokinase increased non-significantly. Immune cells infiltration and increased intra alveolar space were observed in lungs tissue, while alterations were also observed in pancreas of AR treated animals. The induction of AR led to the diabetogenic changes to rats via exerting multifaceted metabolic defects in the biochemical machinery regulating glucose homeostasis.