National Jewish Health

About: National Jewish Health is a healthcare organization based out in Denver, Colorado, United States. It is known for research contribution in the topics: Asthma & T cell. The organization has 883 authors who have published 833 publications receiving 79201 citations. The organization is also known as: National Jewish Medical and Research Center.

Complex and dynamic redistribution of NF-κB signaling intermediates in response to T cell receptor stimulation

Abstract: The central zone of the supramolecular activation cluster (c-SMAC) is a zone of T cell receptor (TCR) enrichment that forms at a T cell/antigen-presenting cell (APC) junction in response to antigen stimulation. We demonstrate that there is a surprisingly complex relocalization process that brings PKCθ and Bcl10, two intermediates in TCR activation of NF-κB, to the cytoplasmic face of the c-SMAC. TCR activation causes enrichment of PKCθ at the c-SMAC, followed by Bcl10 relocalization to punctate cytoplasmic structures, often at sites distant from the c-SMAC. These Bcl10 structures then undergo further relocalization, becoming enriched at the c-SMAC. TCR activation of NF-κB therefore involves the dynamic relocalization of multiple signaling intermediates, with distinct phases proximal to and distant from the c-SMAC.

The role of endothelin-1 in the pathogenesis of idiopathic pulmonary fibrosis.

Abstract: The endothelin system participates in a number of critical biologic pathways, including normal wound healing. In addition, emerging basic science, and animal and human data all suggest that endothelin-1 (EDN1, also known as ET-1) is a potentially important contributor in the pathobiology of fibrosing disorders, including those that affect the lung. For example, EDN1 drives fibroblast activation, proliferation, as well as differentiation into myofibroblasts - processes that lead to excessive collagen deposition. Patients with idiopathic pulmonary fibrosis (IPF) have increased levels of EDN1 in both their bronchoalveolar lavage fluid and lung tissue. Beyond this, rodent models suggest that endothelin receptor antagonists can limit bleomycin-induced lung fibrosis. This suggests a biologic rationale for the blockade of EDN1 to limit the evolution of lung fibrosis in humans. Initial results from a trial examining the efficacy of a dual endothelin receptor antagonist suggest that this approach may delay disease progression in a subset of patients with IPF.

Role of gammadelta T cells in protecting normal airway function

Abstract: Since their discovery 15 years ago, the role of γδ T cells has remained somewhat elusive. Responses of γδ T cells have been found in numerous infectious and non-infectious diseases. New evidence points to γδ T cells' functioning in the airways to maintain normal airway responsiveness or tone. In the lung, distinct subsets of γδ T cell subsets seem to have specific roles, one subset promoting allergic inflammation, the other serving a protective role.

CD23 Deficient Mice Develop Allergic Airway Hyperresponsiveness Following Sensitization with Ovalbumin

Abstract: The low affinity receptor for IgE (CD23) is reported to regulate immune and inflammatory events and as a result, it may have a role in the development of allergic airway inflammation and hyperresponsiveness (AHR). To test this hypothesis CD23-deficient mice were studied following different modes of allergic sensitization. Mice were actively sensitized either intraperitoneally with ovalbumin (OA)/alum or via the airways (10 days exposure to OA aerosol with no adjuvant). Passive sensitization was performed by intravenous injections of OA-specific IgE. Airway responsiveness, serum IgE and IgG levels were assessed together with airway inflammation. Passive sensitization followed by airway challenges resulted in increased OA-specific IgG and IgE in the serum of wild-type mice only, while both the CD23+ / + and CD23− / − groups developed tracheal smooth muscle hyperresponsiveness to electrical field stimulation, indicating that IgE/CD23-mediated immune functions may not be necessary for the development of aller...

Stem cell factor augments Fc epsilon RI-mediated TNF-alpha production and stimulates MAP kinases via a different pathway in MC/9 mast cells.

Abstract: Mast cells express the receptor tyrosine kinase kit/stem cell factor receptor (SCFR) which is encoded by the proto-oncogene c-kit. Ligation of SCFR induces its dimerization and activation of its intrinsic tyrosine kinase activity leading to activation of Raf-1, phospholipases, phosphatidylinositol 3-kinase, and extracellular signal-regulated kinases. However, little is known about the downstream signals initiated by SCFR ligation except for activation of extracellular signal-regulated kinases. The murine mast cell line, MC/9, synthesizes and secretes TNF-alpha following the aggregation of high affinity Fc receptors for IgE (Fc epsilonRI). Ligation of SCFR or Fc epsilonRI on MC/9 cells resulted in the activation of all three MAP kinase family members, extracellular signal-regulated kinases, c-Jun amino-terminal kinase (JNK), and p38. Stem cell factor (SCF)-induced activation of JNK and p38 was insensitive to wortmannin, cyclosporin A, and FK506 whereas activation of these kinases through Fc epsilonRI was sensitive to these drugs. Coligation of SCFR augmented Fc epsilonRI-mediated activation of MAP kinases, especially JNK activation, and SCF augmented Fc epsilonRI-mediated TNF-alpha production in MC/9 cells, although SCF alone did not induce TNF-alpha production. This augmentation by SCF was regulated at the level of transcription, at least in part, since the promoter activity of TNF-alpha was enhanced following addition of SCF. These results demonstrate that SCF can augment Fc epsilonRI-mediated JNK activation and cytokine gene transcription but via pathways that are regulated differently than the ones activated through Fc epsilonRI.