Spred-1 negatively regulates allergen-induced airway eosinophilia and hyperresponsiveness.
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.
Inoue
Hiromasa
H
Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan. inoue@kokyu.med.kyushu-u.ac.jp
Kato
Reiko
R
Fukuyama
Satoru
S
Nonami
Atsushi
A
Taniguchi
Kouji
K
Matsumoto
Koichiro
K
Nakano
Takako
T
Tsuda
Miyuki
M
Matsumura
Mikiko
M
Kubo
Masato
M
Ishikawa
Fumihiko
F
Moon
Byoung-gon
BG
Takatsu
Kiyoshi
K
Nakanishi
Yoichi
Y
Yoshimura
Akihiko
A
D048868:Adaptor Proteins, Signal Transducing; D000403:Airway Resistance; D000818:Animals; D001249:Asthma / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D017931:DNA Primers; D004802:Eosinophilia / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006967:Hypersensitivity / Q000378:metabolism*; D007150:Immunohistochemistry; D015848:Interleukin-5 / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D012097:Repressor Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D016207:Cytokines; D017931:DNA Primers; D015848:Interleukin-5; D012097:Repressor Proteins; C433763:Spred1 protein, mouse; D048049:Extracellular Signal-Regulated MAP Kinases