Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Allergic conjunctivitis (AC) is a common allergic eye disease characterized by clinical symptoms such as itchiness, conjunctival congestion, elevated Ag-specific IgE, mast cell activation, and local eosinophil infiltration. In this study we established a murine model for Ag-induced AC to understand the pathogenesis of the disease. Cell transfer experiments indicated that AC can be divided into early and late phase responses (EPR and LPR). EPR was associated with IgE responses, leading to itchiness, whereas LPR was characterized by local eosinophil infiltration. Both EPR and LPR were significantly inhibited in STAT6-deficient mice, and adoptive transfer of Th2 cells reconstituted LPR. Furthermore, SOCS3 was highly expressed at the disease site, and T cell-specific expression of SOCS3 deteriorated clinical and pathological features of AC, indicating that Th2-mediated SOCS3 expression controls the development and persistence of AC. Reduction of the expression level in SOCS3 heterozygous mice or inhibition of function in dominant-negative SOCS3 transgenic mice clearly reduced the severity of AC. In contrast, constitutive expression of SOCS5, a specific inhibitor of IL-4 signaling, resulted in reduced eosinophil infiltration. These results suggest that negative regulation of the Th2-mediated response by dominant-negative SOCS3 and SOCS5 could be a target for therapeutic intervention in allergic disease.
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PMID:The control of allergic conjunctivitis by suppressor of cytokine signaling (SOCS)3 and SOCS5 in a murine model. 1621 Jun 57

Atopic dermatitis, allergic rhinitis, and bronchial asthma are allergic immune disorders characterized by a predominance of T helper 2 (Th2) cells, the resulting elevation of allergen-specific immunoglobulin E (IgE), and mast cell- and eosinophil-associated inflammation. The cytokine environment at the site of the initial antigen stimulation determines the direction of helper T-cell differentiation into Th1 or Th2 cells. Therefore, negative regulators of cytokine signaling, suppressors of cytokine signaling (SOCS) proteins, play an important role in Th2-mediated allergic responses through the control of the balance between Th1 and Th2 cells. SOCS3 and SOCS5 are predominantly expressed in Th2 and Th1 cells, respectively, and they reciprocally inhibit the Th1 and Th2 differentiation processes. In this article, we discuss the role of SOCS3 and SOCS5 proteins in atopic asthma and allergic conjunctivitis and explore the potential of SOCS proteins as targets for therapeutic strategies in allergic disorders.
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PMID:Suppressor of cytokine signaling 3 (SOCS3) in Th2 cells evokes Th2 cytokines, IgE, and eosinophilia. 1647 92