Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of IgE antibodies in the initiation of allergen induced release of mediators from sensitised mast cells is discussed; both from the point of view of their binding to the high affinity Fc(epsilon)RI receptor and in their provision of a triggering signal, resultant upon the cross-linking of cell bound IgE molecules by specific antigen (allergen). A possible inter-relationship between the Fc(epsilon)RI and a low affinity receptor for the IgG4 isotype on human mast cells is considered, in the light of evidence that the two types of receptor could be acting synergistically in certain clinical allergy situations (e.g. atopic eczema). It is suggested that a similar juxta-positioning of Fc(gamma 4)RII and Fc(epsilon)RI receptors on human B-lymphocytes might provide scope for regulation of IgE synthesis by IgG4 auto-antibodies directed against this immunoglobulin isotype.
Mol Immunol 1988 Nov
PMID:Inter-receptor relationships in effector cell triggering, with particular reference to the mast cell. 297 63

Eleven axillary lymph nodes from patients with different cutaneous disorders (systemic scleroderma, atopic eczema, psoriasis, hairy cell erythroderma, dermatopathic lymphadenitis) were examined by electron microscopy. In systemic scleroderma interdigitating cells (IDC's) showed typical ultrastructural features as well as intimate contacts with neighboring lymphocytes. In atopic eczema IDC's were characterized by widespread invaginations of the cell membrane, and an increase in tubulo-vesicular structures and microfilaments. Similar observations have been made in dermatopathic lymphadenitis. In psoriasis and hairy cell erythroderma. IDC's showed only a few interdigitations and invaginations of the cell surface. It is supposed that these structural changes in IDC's reflect the different immunological conditions of the diverse cutaneous disorders.
Virchows Arch B Cell Pathol Incl Mol Pathol 1980
PMID:Ultrastructural differences of interdigitating cells in human lymph nodes. 610 48

In a series of transgenic mice, the human tissue collagenase gene was expressed in the suprabasal layer of the skin epidermis. Visually, the mice had dry and scaly skin which upon histological analysis revealed acanthosis, hyperkeratosis, and epidermal hyperplasia. At the ultrastructural level, intercellular granular materials were absent in the transgenic skin epidermis but contact was maintained through the intact desmosomes. Despite a diversity of underlying etiologies, similar morphological hyperproliferative changes in the epidermis are observed in the human skin diseases of lamellar ichthyosis, atopic dermatitis, and psoriasis. Subsequent experiments demonstrate that when the transgenic mouse skin was treated once with an initiator (7,12-dimethyl-benz[a]anthracene) and then twice weekly with a promoter (12-O-tetradecanoylphorbol-13-acetate), there was a marked increase in tumor incidence among transgenic mice compared with that among control littermates. These experiments demonstrate that by overexpressing the highly specific proteolytic enzyme collagenase, a cascade of events leading to profound morphological changes which augment the sensitivity of the skin towards carcinogenesis is initiated in the epidermis.
Mol Cell Biol 1995 Oct
PMID:Collagenase expression in transgenic mouse skin causes hyperkeratosis and acanthosis and increases susceptibility to tumorigenesis. 756 25

Interleukin 5 (IL-5) is a T-cell lymphokine known to stimulate development, functional activity, and in vitro survival of eosinophils. Tissue and blood eosinophilia occurring during allergic responses of the immune system are potentially mediated by IL-5 secreting T-cells. To test this hypothesis a series of allergen-specific T-cell clones were established from peripheral blood and skin lymphocytes of patients with atopic dermatitis and house dust mite sensitization. In addition, alloreactive T-cell clones were also prepared from peripheral blood lymphocytes of healthy donors. Cloned T-cells were analyzed for IL-5 mRNA expression and IL-5 secretion by means of in vitro gene amplification using the reverse transcriptase polymerase chain reaction and IL-5 specific oligonucleotide hybridization, as well as IL-5-specific ELISA. A majority of allergen-specific long-term cultured T-cell clones (84%) of different donors and of either phenotype (CD8+ or CD4+) disclosed IL-5 transcripts on stimulation with lectins. Almost all clones exhibiting IL-5 transcripts also released immunoreactive IL-5 protein into their culture supernatants. In contrast, only 2% of alloreactive T-cell clones obtained from healthy donors and none of alloreactive T-cell clones of one atopic patient investigated expressed detectable amounts of IL-5 mRNA in response to lectin stimulation, all of whom were CD4+. These results suggest that eosinophilia observed in allergic responses in the peripheral blood and in tissues at the site of induced late-phase cutaneous reaction may be associated with IL-5 release by allergen-specific T-cells.
J Mol Med (Berl) 1995 Feb
PMID:Interleukin 5 expressing allergen-specific T-lymphocytes in patients with house dust mite sensitization: analysis at a clonal level. 941 Apr 77

Until recently it was believed that the T cell response of atopic dermatitis patients challenged with inhalant allergens originates almost exclusively and specifically from Th2 cells capable of secreting an abundance of interleukin (IL)-4 while producing no interferon (IFN)-gamma. To reevaluate this concept in a large cohort of atopic dermatitis patients we established 177 CD4+ T cell clones (45 of which showed specificity for house dust mite antigen) from the peripheral blood (n = 76), naturally occurring skin lesions (n = 40), and allergen-exposed skin (n = 61) of different patients. These clones were examined for their capacity to secrete IL-4 and IFN-gamma upon mitogenic stimulation. Moreover, 20 of these T cell clones were investigated for the synthesis of transcripts for IL-5, another Th cytokine. Our results indicate that the majority (52-100%) of allergen-specific T cells in both skin and blood of atopic individuals failed to exhibit a restricted cytokine secretion pattern and thus were classified as Th0 cells. House dust mite antigen specific T cells displaying a restricted secretion pattern (n = 16) were either of the Th1 or the Th2 type. Specific Th2 cells, however, were found almost exclusively in allergen patch test reactions, indicating that the Th2 differentiation pathway is seen preferentially in allergen-exposed skin. The cytokine secretion profile of T cell clones obtained from naturally occurring skin lesions showed similarity to those of patch test lesion, suggesting that the patch test represents a useful model to investigate the pathogenesis of atopic dermatitis.
J Mol Med (Berl) 1996 Jul
PMID:Comparative analysis of the frequency of house dust mite specific and nonspecific Th1 and Th2 cells in skin lesions and peripheral blood of patients with atopic dermatitis. 884 52

Understanding the induction and regulation of IgE synthesis in human B cells is crucial to elucidate the molecular pathogenesis of IgE-dependent diseases. Experimental data, in part supported by clinical observations, suggests that IgE regulation is a complex process involving several cellular and molecular interactions. A two-signal model is accepted for the induction of IgE synthesis in human B cells. The first signal is provided by the cytokines interleukin 4 or 13, which are secreted by T cells, mast cells, and basophils. The second signal for the induction of IgE synthesis requires cell contact between T and B cells. Engagement of the B cell antigen CD40 by the CD40 ligand (CD40L) expressed on T cells leads to subsequent isotype switching during immunoglobulin synthesis in B cells. The CD40-CD40L interaction is well established as a key signal for the induction of isotype switching while the elucidation of the role of other cell-cell interactions, for example, through adhesion molecules, needs further study. An important counteracting cytokine for IgE synthesis is interferon (IFN) gamma which is produced mainly by T lymphocytes. Several cell-contact molecules, cytokines, and various hormones have been shown to modulate IgE synthesis in vitro, suggesting a complex network of molecular events to be involved in the production of IgE. However, the relevance of these factors for IgE production in vivo requires further elucidation. Here we describe the molecular mechanisms known to be involved in the induction and regulation of human IgE synthesis and discuss the role of various molecules during this process. Furthermore, evidence is presented that the understanding of IgE synthesis provides a potential key for new therapeutic strategies in patients with IgE mediated diseases including atopic dermatitis.
J Mol Med (Berl) 1997 Jun
PMID:Molecular regulation of human IgE synthesis. 923 84

Similar to interleukin-3 (IL-3), IL-5, and granulocyte macrophage colony-stimulating factor (GM-CSF), IL-4 can be secreted by several cell types involved in allergic inflammatory reactions, and therefore can affect eosinophil function similarly. In this study, we investigated the presence of an IL-4 receptor (IL-4R) on human eosinophils. When two different monoclonal antibodies (mAbs) against the IL-4R alpha-chain (IL-4Ralpha) were used, fluorescent-activated cell sorter analysis revealed the presence of an IL-4Ralpha on both eosinophils of normal donors and atopic dermatitis patients. In addition, the expression of the IL-2R gamma-chain, a functional component of the IL-4R in some cell types, was demonstrated. The IL-4Ralpha appeared to be expressed constitutively, and stimulation with cytokines IL-2, IL-3, IL-5, GM-CSF, and interferon-gamma did not further increase IL-4Ralpha expression. Evidence for an IL-4Ralpha was further substantiated by mRNA analysis. Both Northern blot analysis and reverse transcriptase/polymerase chain reaction revealed the presence of mRNA for the IL-4Ralpha in eosinophils from normal individuals and AD patients. Furthermore, we demonstrated that both IL-4 and IL-13 were capable of inducing PI-3 kinase activity in human eosinophils. Because this activation could be inhibited by an IL-4Ralpha mAb, we conclude that both cytokines can activate human eosinophils through binding to a receptor complex comprising the IL-4Ralpha and-yet to be identified-associated proteins. In addition, the involvement of IL-4 in functional responses was studied. IL-4 appeared to "prime" eosinophils to respond chemotactically toward regulated on activation, normal T cells expressed and secreted, but did not affect platelet-activating factor-induced chemotaxis. Taken together, these data show the presence of a functional IL-4R on human eosinophils.
Am J Respir Cell Mol Biol 1998 Oct
PMID:Human eosinophils constitutively express a functional interleukin-4 receptor: interleukin-4 -induced priming of chemotactic responses and induction of PI-3 kinase activity. 976 67

Macrophage migration inhibitory factor (MIF) was the first T-cell-derived soluble lymphokine to be identified. It was originally found to inhibit the migration of macrophages and activate them at inflammatory loci. During the past few years, however, previously unrecognized properties of MIF have been discovered. It also functions, for example, as a pituitary hormone, glucocorticoid-induced immunomodulator and isomerase. We cloned rat MIF cDNA and reported that the nucleotide sequence of the cDNA predicts a protein consisting of 114 amino acids. Northern blot analysis indicated that the MIF mRNA was expressed in a wide variety of organs, including the brain, kidney, and liver. Following this, we demonstrated definitively that MIF was expressed in a variety of cells, suggesting its involvement in various biological events such as wound healing, atopic dermatitis, and, possibly, diabetes/obesity. Furthermore, we elucidated its physicochemical properties, including the tertiary structures of both human and rat MIF. These tertiary structures showed that this protein forms a homotrimer with each monomer consisting of two beta/alpha/beta motifs, thus resembling 5-carboxymethyl-2-hydroxymuconate isomerase and d-dopachrome tautomerase. From the available data on MIF, including ours, it is considered that the protein is associated not only with immune responses but also with cell growth and differentiation during wound repair and carcinogenesis. Thus, MIF could become a major target protein in a variety of pathophysiological states and anti-MIF antibodies and antagonists could be applied therapeutically in the clinical situation for treatment of various diseases. Bearing this in mind, this review discusses the role of MIF, considering its gene and protein structures as well as its pathophysiological functions in various organs and disease states, finally considering perspectives for the future.
Int J Mol Med 1998 Jul
PMID:Novel pathophysiological aspects of macrophage migration inhibitory factor (review). 985 38

The CD5/Leu-1 is involved in the activation of the T-cell helper function through T/B-cell collaboration by CD5/CD72 interaction. T-cell function is known to be dysregulated in atopic dermatitis. However, to date, the role of CD5 has not been investigated in atopic dermatitis, nor has the presence of circulating soluble CD5 been reported in atopic dermatitis. Five patients with atopic dermatitis who showed typical symptoms, 5 acute febrile patients and 5 normal subjects were tested. Peripheral blood mononuclear cells and plasma were separated. The T- and B-cells were separated using immunomagnetic beads. Reverse transcription polymerase chain reaction was performed using CD5 specific primers. Immunoblotting with the mouse antiCD5 monoclonal antibody was done. Circulating soluble CD5 was present only in 4 out of 5 atopic patients. However, it was not detected in acute febrile patients nor in normal subjects. CD5 mRNA expression was detected in all atopic patients and acute febrile patients. CD5 mRNA expression in T- and B-cells was tested in patients with atopic dermatitis and was detected only in the T-cells. In this study, circulating soluble CD5 was detected in atopic patients and soluble CD5 was suspected to participate in the pathogenesis of atopic dermatitis. CD5 mRNA expression was detected only in T-cells, which suggests that circulating soluble CD5 might be produced from T-cells.
Mol Cells 1998 Oct 31
PMID:Circulating soluble CD5 in atopic dermatitis. 985 51

Eosinophils have been implicated in a broad range of diseases, notably allergic conditions (for example, asthma, rhinitis and atopic dermatitis) and other inflammatory disorders (for example, inflammatory bowel disease, eosinophilic gastroenteritis and pneumonia). These disease states are characterized by an accumulation of eosinophils in tissues. Severe tissue damage ensues as eosinophils release their highly cytotoxic granular proteins. Defining the mechanisms that control recruitment of eosinophils to tissues is fundamental to understanding these disease processes and provides targets for novel drug therapy. An important discovery in this context was the identification of an eosinophil-specific chemoattractant, eotaxin. Over the past six years there has been intensive investigation into the biological effects of eotaxin and its role in specific disease processes and this is the subject of this review.
Mol Med Today 2000 Jan
PMID:Eotaxin and eosinophil recruitment: implications for human disease. 1063 71


1 2 3 4 5 6 7 8 9 10 Next >>