Spred-1 Negatively Regulates Allergen-induced Airway Eosinophilia and Hyperresponsiveness

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2005 Jan 5

PMID 15630138

Citations 35

Authors

Hiromasa Inoue

Reiko Kato

Satoru Fukuyama

Atsushi Nonami

Kouji Taniguchi

Koichiro Matsumoto

Takako Nakano

Miyuki Tsuda

Mikiko Matsumura

Masato Kubo

Fumihiko Ishikawa

Byoung-Gon Moon

Kiyoshi Takatsu

Yoichi Nakanishi

Akihiko Yoshimura

Affiliations

Soon will be listed here.

Abstract

T helper 2 cytokines, including interleukin (IL)-4, IL-5, and IL-13, play a critical role in allergic asthma. These cytokines transmit signals through the Janus kinase/signal transducer and activator of transcription (STAT) and the Ras-extracellular signal-regulated kinase (ERK) signaling pathways. Although the suppressor of cytokine signaling (SOCS) family proteins have been shown to regulate the STAT pathway, the mechanism regulating the ERK pathway has not been clarified. The Sprouty-related Ena/VASP homology 1-domain-containing protein (Spred)-1 has recently been identified as a negative regulator of growth factor-mediated, Ras-dependent ERK activation. Here, using Spred-1-deficient mice, we demonstrated that Spred-1 negatively regulates allergen-induced airway eosinophilia and hyperresponsiveness, without affecting helper T cell differentiation. Biochemical assays indicate that Spred-1 suppresses IL-5-dependent cell proliferation and ERK activation. These data indicate that Spred-1 negatively controls eosinophil numbers and functions by modulating IL-5 signaling in allergic asthma.

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