Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0241981 (loss of balance)
 452 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Allergic lung diseases such as atopic asthma and extrinsic allergic alveolitis are now recognized as chronic inflammatory lung diseases promoted by dysregulation of T cell-mediated immune mechanisms. The basis of this regulation and the impact of the atopic status of these individuals on this chronic inflammatory disease have yet to be fully explained. The studies described in this paper reveal mechanisms of macrophage lymphocyte interaction in which evidence is presented that a balance of functionally distinct macrophage subsets needs to be maintained to regulate T cell reactivity in the lung. Similarly a balance within the T cell populations may influence and regulate the relative proportions of functionally distinct macrophages. Investigations of bronchoalveolar lavage and biopsy from patients with allergic lung disease have revealed a gross imbalance within the lung macrophage populations and an associated dysregulation in T cell stimulation. In vitro studies have revealed that imbalances in the macrophage populations may lead to changes in local level of cytokine production specifically TGF-beta which would then impact on the control of T cell populations. Conversely aberrant development of activated T cells with a TH2-like cytokine repertoire may influence the balance of macrophages. Our in vitro studies have revealed that macrophage phenotype and function can be modulated in vitro by contact with T cell-derived cytokines and that this change in phenotype is reflected in a change in function. These data support the hypothesis that components of the immune system normally associated with allergic reactions may be stimulated in the absence of any overt atopic reactivity in the individual concerned. Thus immediate type allergic reactions may represent a "super-imposed" burden [provocating factor] in atopic individuals but the underlying immunopathogenesis of these diseases may not be dependent on this state of immediate type hypersensitivity. It is concluded that the loss of balance within functional distinct macrophage populations within the lung may represent the fundamental problem in allergic lung disease. This possibility is discussed in the light of other work in this field.
 ...
PMID:Macrophages and allergic lung disease. 893 58

The role is described of soluble type I p55 and type II p75 TNF receptors (sTNF-R) in the development of septic syndrome (SS). It is assumed, that at an early stage of infection, high levels of sTNF-R p55 and p75 augment systemic immunity and enhance the natural non-specific response. At the same time the presence of TNF-? in plasma proves inadequate secretion of sTNF-R p55 and p75 that is insufficient to block its generation and neutralization during SS. The concentration of sTNF-R p55 increases mainly at an early stage of infection, whereas p75 level rises constantly. High levels of p75 in the group of animals which survived may suggest that it is a more potent TNF-alpha cytotoxicity inactivator than the p55 form. This process occurs by means of blocking ligand bonds of TNF-alpha with its superficial effector cell receptor. These considerations lead to the conclusion that for the prognosis in septic syndrome, an incomparably greater role than absolute TNF-alpha concentration is played by the quantitative ratio of this cytokine to its soluble receptors. High values of TNF-alpha to sTNF-R ratio, especially to its p55 form, suggest loss of balance between the number of ligand bonds of cytokines and the activity of their inhibitors and usually come with poor prognosis and lack of efficient SS treatment. Soluble TNF receptors are physiological factors that inhibit TNF-alpha activity, the effect of which may be compared to that of monoclonal anti-TNF-alpha antibodies.
 ...
PMID:[Soluble TNF p55 and p75 receptors in the development of sepsis syndrome]. 1271 35

Multiple sclerosis (MS) is a chronic autoimmune disease, and the most common cause of nontraumatic disability in young people. The etiology of this disease is not well defined yet. Cytokines play an important role in differentiation, maturation and survival of a wide range of cells, including cells of the immune system. Suppressor of cytokine signaling (SOCS) proteins are the most important regulators of this cytokine signaling pathway. The aim of present study was to compare the expression levels of SOCS1, SOCS2, SOCS3 and SOCS5 genes in the blood of 50 relapsing-remitting MS (RR-MS) patients and 50 healthy controls by Taqman Quantitative Real-Time PCR in patients and healthy control group. We observed that SOCS1 and SOCS5 expression was significantly down-regulated (P=0.045 and P=0.044, respectively); whereas, no significant difference was observed between MS patients and controls for SOCS2 and SOCS3 gene expression (P=0.747 and P=0.439, respectively). In addition, there was no significant correlation between the expression of SOCS1, SOCS2, SOCS3 and SOCS5 genes and clinical findings, such as the level of physical disability in the MS patients according to the Kurtzke Expanded Disability Status Scale (EDSS) criterion and disease duration. However, a significant positive correlation was observed between expression levels of SOCS genes. This study shows that loss of balance among various members of the SOCS family proteins may contribute to pathophysiology of multiple sclerosis.
 ...
PMID:SOCS gene family expression profile in the blood of multiple sclerosis patients. 2825 52

Interleukin 33 (IL-33) is highly expressed in barrier sites, acting via the suppression of tumorigenicity 2 receptor (ST2). IL-33/ST2 axis has long been known to play a pivotal role in immunity and cell homeostasis by promoting wound healing and tissue repair. However, it is also involved in the loss of balance between extensive inflammation and tissue regeneration lead to remodeling, the hallmark of fibrosis. The aim of the current review is to critically evaluate the available evidence regarding the role of the IL-33/ST2 axis in organ fibrosis. The role of the axis in tissue remodeling is better understood considering its crucial role reported in organ development and regeneration. Generally, the IL-33/ST2 signaling pathway has mainly anti-inflammatory/anti-proliferative effects; however, chronic tissue injury is responsible for pro-fibrogenetic responses. Regarding pulmonary fibrosis mature IL-33 enhances pro-fibrogenic type 2 cytokine production in an ST2- and macrophage-dependent manner, while full-length IL-33 is also implicated in the pulmonary fibrotic process in an ST2-independent, Th2-independent fashion. In liver fibrosis, evidence indicate that when acute and massive liver damage occurs, the release of IL-33 might act as an activator of tissue-protective mechanisms, while in cases of chronic injury IL-33 plays the role of a hepatic fibrotic factor. IL-33 signaling has also been involved in the pathogenesis of acute and chronic pancreatitis. Moreover, IL-33 could be used as an early marker for ulcer-associated activated fibroblasts and myofibroblast trans-differentiation; thus one cannot rule out its potential role in inflammatory bowel disease-associated fibrosis. Similarly, the upregulation of the IL-33/ST2 axismay contribute to tubular cell injury and fibrosis via epithelial to mesenchymal transition (EMT) of various cell types in the kidneys. Of note, IL-33 exerts a cardioprotective role via ST2 signaling, while soluble ST2 has been demonstrated as a marker of myocardial fibrosis. Finally, IL-33 is a crucial cytokine in skin pathology responsible for abnormal fibroblast proliferation, leukocyte infiltration and morphologic differentiation of human endothelial cells. Overall, emerging data support a novel contribution of the IL-33/ST2 pathway in tissue fibrosis and highlight the significant role of the Th2 pattern of immune response in the pathophysiology of organ fibrosis.
 ...
PMID:IL-33/ST2 Axis in Organ Fibrosis. 3040 26