IL-6 Inhibitor Induction in Coculture Of Bronchial Epithelial Cells and Eosinophils

IL-6 Inhibitor
Eosinophil infiltration of the mucosa is a feature of asthmatic airways. Their adhesion to bronchial epithelial cells has been proposed to lead to the generation of inflammation mediators which may contribute to asthma pathology. Bronchial epithelial cells (BEAS-2B cell line) and peripheral blood eosinophils were cultured alone or in combination and the production of an inflammatory cytokine, IL-6, was measured. IL-6 was produced principally by epithelial cells and the production was enhanced more than 10-fold in the presence of eosinophils. Significant augmentation of epithelial IL-6 production persisted even when eosinophils were fixed with paraformaldehyde. The eosinophil-induced IL-6 production was extensively inhibited by inhibitors of p38 mitogen-activated protein (MAP) kinase or nuclear factor ??B (NF??B). (more…)

Histamine Type-2 Receptor as Major Player in Peripheral Tolerance

histamine receptor
Histamine is a low-molecular-weight monoamine that binds to four different G-protein-coupled receptors, and has recently been demonstrated to regulate several essential events in the immune response. The histamine receptor type 2 (HR2) is coupled to adenylate cyclase and studies in different species and several human cells have demonstrated that inhibition of characteristic features of the cells by primarily cAMP formation dominates in HR2-dependent effects of histamine. (more…)

Regulatory T Cells (Treg) Therapeutic Application

treg
An emerging concept is that pro-inflammatory signals lead to loss of Regulatory T Cells (Treg) function. Pasare and Medzhitov (2003) demonstrated that activation of DCs through TLRs led to the production of signals, including IL-6, which blocked the suppressive effect of CD4+CD25+ Treg. Subsequent studies support these observations. For example in a mouse model of allergic airway disease, IL-6 is proposed to act via two mechanisms to promote disease: direct enhancement of Th2 responses and by overcoming the suppressive function of CD4+CD25+ Treg. Tumor necrosis factor (TNF) as well as IL-7 and IL-15 have also been proposed to overcome regulatory activity in other human immunologic diseases. (more…)

Foxp3 Forkhead Winged Transcription Factor & Mechanisms Of Suppression

foxp3
The intracellular forkhead winged transcription factor Foxp3 (forkhead box P3) appears to be specifically expressed by naturally occurring Treg cells, particularly in mice, although in humans there is evidence of upregulation of Foxp3 in all T cells on activation. Foxp3 is required for the development and function of naturally occurring regulatory t cells (treg) and expression is sufficient to convert non-regulatory CD4+CD25T cells into cells with regulatory activity. Conversion of peripheral CD4+CD25 naive T cells to Foxp3+CD4+CD25 foxp3+ Treg cells can be induced by TGF-ß. In a murine asthma model, these TGF-ß-induced Treg prevented house-dust mite-induced allergic pathogenesis or infection pathogenesis in lungs. A single independent report has suggested that IL-4 and IL-13 also induce Foxp3+CD25+ Treg from CD4+CD25precursors. (more…)

Bacterial Lipopolysaccharide and Humoral Factors Immune Systems

bacterial lipopolysaccharide
One especially favored target for immune recognition is bacterial lipopolysaccharide (LPS). This macromolecule is found only in the outer lipid bilayer that surrounds the cell walls of gram-negative bacteria, such as Neisseria, Salmonella, and Escherichia coli. Each molecule of bacterial lipopolysaccharide consists of a core carbohydrate linked on one side to a phospholipid (called lipid A) that is anchored in the bilayer and on the other side to a long polysaccharide chain (called the O sidechain) that extends outward from the bacterial surface (Figure 1 bellow). The sequence of sugars making up the O sidechain is species-specific and highly variable, even within a single bacterial genus: For example, more than 1000 variants in Salmonella are known. (more…)

Peptide Antibiotics and Defensins Amino Acids

peptide antibiotics
Other humoral effectors and humoral factors have the ability to lyse microorganisms directly. The best studied of these are a class of small peptide antibiotics known as defensins, which in their active forms are all roughly 30 amino acids long (3,5 kilodaltons), positively charged, and protease-resistant. Each also has three internal disulfide bonds. They are classified as either α or β defensins based on the arrangement of the disulfides, but both classes have nearly the same compact, folded structure consisting of three strands of antiparallel β-pleated sheets. (more…)

The Jak/Stat Signaling Pathway

jak/stat pathway
Perhaps the most exciting recent advance in the cytokine signaling field has been the elucidation of the Jak/Stat pathway. The Janus kinase (Jak) family consists of four known enzymes (Jak1, Jak2, Jak3, and Tyk2), each of which associates specifically with the cytoplasmic tails of one or more cytokine receptor subunits. For example, IL-2R associates with both Jak1 and Jak3, which bind its α and γ subunits, respectively. Cytokine binding brings the receptor subunits together and allows the associated Jak proteins to phosphorylate and activate one another. The primary substrates of the activated Jaks are a family of transcription factors called the Stat (for signal transducers and activators of transcription) proteins. The Stat proteins contain SH2 domains and so are recruited to the vicinity of an activated receptor when its kinases become active. (more…)

Leukocyte Chemotactic Factors

Once it is tethered onto the venule wall, the neutrophil or other leukocyte comes into contact with a wide variety of inflammatory mediators that may either be expressed by the activated endothelium or simply diffuse into the blood from the injured tissue. Among these mediators are a diverse subset of intermediaries known as leukocyte chemotactic factors which bind to receptors on the leukocyte surface and trigger the second, activation phase of margination. (more…)

Inflammation Mediators and Vascular Responses to Injury or Infection

inflmmation responses
Some of the immediate sequelae of injury are uncomfortably familiar: Soon after an injury occurs, the affected site and its surrounding tissues become reddened, warm, swollen, and painful. These four signs which are probably the most useful and ubiquitous diagnostic clues in all of clinical medicine are hallmarks of acute inflammation, the body’s initial physiologic reaction to tissue distress. In its simplest form, inflammation is a response carried out by blood vessels and by the endothelial cells that line them. (more…)

Antimicrobial Enzymes and Binding Proteins

antimicrobial enzymes
A few of the best known humoral effectors of innate immunity are listed in Table 1 bellow, along with the types of target molecules they recognize. Some are enzymes that can directly injure or kill microbial pathogens. An example is lysozyme, an endoglycosidase found in human saliva, mucus, tears, and other secretions, which attacks the protective cell wall encasing every bacterial cell. Lysozyme acts by digesting the peptidoglycan meshwork formed by long carbohydrate chains of alternating N-acetylmuramic acid and N-acetylglucosamine residues, crosslinked covalently by short oligopeptide sidechains which is a major constituent of all bacterial cell walls but is not found in mammalian tissues. (more…)

Next Page »