Current Drug Targets - Inflammation & Allergy - Volume 4, Issue 2, 2005

Nitrosative stress and nitration of proteins in airway epithelium maybe responsible for steroid resistance in asthma and steroid ineffectiveness in chronic obstructive pulmonary disease (COPD), supporting the potential role of future therapeutic strategies aimed at regulating NO synthesis in asthma and COPD (for example, combination treatment with NOS inhibitors and corticosteroids). Here, the potential role of NO modulat Read More

In recent years, significant progress has been made in understanding the involvement of pro-inflammatory lipidic mediators in the pathogenesis of allergic diseases. The most relevant lipidic mediator is arachidonic acid and its metabolites. Arachidonic acid is the precursor for biosynthesis of eicosanoids, potent mediators of inflammation that have been implicated in the pathogenesis of diverse disease processes. Eicosanoids Read More

Essential role of β2-adrenoreceptor (β2AR) in airway relaxation is well established. Nevertheless, β2AR seems playing an actual role in allergy and inflammation. Interaction between β2AR and proinflamatory cytokines in airway smooth muscle has been revealed. Being located on proinflamatory cells, β2ARs may influence function of these cells in vivo. It was clear established, that stimulation of β2AR inhibits releas Read More

Asthma, atopic dermatitis, allergic rhinitis, which are amongst the most clinically relevant allergic disorders in industrialized countries affecting hundreds of millions of people world-wide, are characterized by tissue infiltration of Th2 cells, eosinophils, mast cells and basophils. Recruitment of these leukocyte subpopulations proceeds in response to specific chemotactic clues produced by tissue resident cells and is further ampli Read More

Innate and adaptive immune responses evolve as protective mechanisms against infectious microorganisms in humans. CD14 and tolllike receptors (TLRs) are examples of pattern recognition receptors that detect antigenic molecules on the surface of gram-positive (peptidoglycans, lipoteichoic acid) and gram-negative (lipopolysaccharide) bacteria. In vitro studies suggest that lipopolysaccharide is a potent inducer of interleukin- Read More

Airway remodeling is a major change responsible for irreversible asthmatic airflow restriction. The Th-2 cytokines-dominant eosinophilic inflammatory mechanism cannot fully explain the progressive subepithelial fibrosis and structural changes in the extracellular matrix (ECM). Matrix metalloproteinases (MMPs) are the key enzymes responsible for ECM degradation. MMPs are normally produced and secreted under the Read More

It has been hypothesized that T cell recognition of a self-antigen in the periphery, can lead to autoimmunity by activating T cells through T cell receptor signaling. However, in order for optimal activation to occur a second signal, termed “costimulation”, has to be delivered by antigen presenting cells to the T cells. Both the T cell receptor and co-stimulatory signals have been specific targets for therapeutic intervention Read More

Human autoimmune disease involves local activation of antigen-specific CD4+ T cells that produce inflammatory Th1 cytokines leading to the further recruitment and activation of lymphocytes and monocytes, resulting ultimately in the destruction of target tissue. Antigen presenting cells (APCs) initiate activation of CD4+ T cells in a multistep process that minimally involves co-ligation of the TCR and CD4 by the MHC class I Read More

Certain members of the TNF-receptor family have shown proinflammatory function during immune activation and can be directly involved with the pathogenic effects observed during an autoimmune episode. The TNF-R family members summarized in this review includes: TNF-RI + II, OX40, and 4-1BB and they are expressed on a variety of leukocytes within the body. Studies within the last decade suggest that all of these proteins Read More

Autoimmune diseases are initiated and maintained by presentation of self antigen through complex interactions between different cells of the immune system. In most autoimmune disorders, autoantigen-specific responses are induced by the activation of specific T cells with self peptides displayed on activated antigen presenting cells (APCs). These T cells may then activate and drive B cell responses that either initiate or c Read More

Vaccination with self peptides contained within T cell receptor (TCR) chains, expressed by pathogenic Th1 cells can induce a second set of regulatory T cells that can reverse paralysis in rodents with experimental encephalomyelitis, and similarly, may have the potential to regulate myelin-reactive Th1 cells in patients with multiple sclerosis (MS). In this review, we discuss our recent discovery that TCR-reactive T cells Read More

The capacity of the pregnancy state to regulate T-cell function is well documented. A consequence of this regulation is that many Tcell mediated autoimmune disorders, including multiple sclerosis (MS) are suppressed during pregnancy. The suppression of MS during pregnancy is more potent than the currently available treatments for this disease. Thus, the study of immunoregulatory factors of pregnancy could potentially res Read More

The role of CD8+ T cells in multiple sclerosis (MS) and its animal models has been enigmatic. Most studies of MS have focused on the role of CD4+ Th1 T cells and many therapeutic strategies have been directed toward ameliorating the activity of this subset. Some of these strategies were effective in experimental autoimmune encephalomyelitis (EAE), a widely used animal model for MS dependent on CD4+ T cells, but para Read More

Alzheimer's disease, the most common neurodegenerative dementia in the elderly, affects cognition, behavior and functioning, and a prominent neuroinflammatory component likely contributes to disease pathogenesis. The epidemiology of AD has previously shown that NSAID use decreases the incidence of AD, and evidence from tissue culture, in vivo models, and Alzheimer brain tissue studies indicate that inflammation in A Read More

Inflammation plays a variable part in the pathogenesis of several spinal disorders. Ankylosing spondylitis is a chronic inflammatory arthropathy of the spine and rheumatoid arthritis, whilst affecting predominantly limb joints, also affects the cervical spine in a significant proportion of people. Inflammation is also involved in disorders such as disc herniation and sciatica, which have previously been thought of as being primarily Read More

The increasing levels of morbidity and mortality due to the rising prevalence of asthma and other allergic diseases have inspired investigations of several new molecular techniques to improve treatment. Recently, several preclinical studies have been published which utilize attributes or facets of DNA to address asthma therapy. These novel therapeutics include antisense oligonucleotides against TH2 cytokines and associated tr Read More