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Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Role of Endogenous Inhibitors of Cytokine Signaling in Allergic Asthma

Author(s): Hiromasa Inoue, Satoru Fukuyama, Koichiro Matsumoto, Masato Kubo and Akihiko Yoshimura

Volume 14, Issue 2, 2007

Page: [181 - 189] Pages: 9

DOI: 10.2174/092986707779313327

Price: $65

Abstract

T helper 2 cytokines, including interleukin (IL)-4, IL-5, and IL-13, play an important role in allergic immune disorders, such as bronchial asthma. These cytokines regulate diverse biological functions by binding to receptors at the cell surface to activate complex signal transduction pathways, including the Janus kinase-signal transducer and activator of transcription (JAK-STAT) and the Ras-extracellular signal-regulated kinase (ERK) signaling pathways. The suppressor of cytokine signaling (SOCS) family proteins has been shown to regulate the JAK-STAT pathway, and the Sprouty-related EVH1-domain-containing protein (SPRED) family proteins regulate the Ras-ERK pathway. SOCS3 and SOCS5 are predominantly expressed in Th2 and Th1 cells, respectively, and they reciprocally inhibit the Th1 and Th2 differentiation processes. SOCS3 also has a role in Th3 differentiation. SPRED-1 is expressed in hematopoietic cells, including eosinophils, and negatively controls the eosinophil numbers and functions by modulating IL-5 signaling. Here, we discuss the role of SOCS and SPRED proteins in allergic asthma and explore the potential of these proteins as targets for therapeutic strategies in allergic asthma.

Keywords: MAP kinase, SOCS proteins, Regulatory T Cells, SPRED-1, Asthma


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