title: Spred-1 negatively regulates allergen-induced airway eosinophilia and hyperresponsiveness.
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.
authors.affiliation: 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
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Inoue
authors.forename: Reiko
authors.initials: R
authors.lastname: Kato
authors.forename: Satoru
authors.initials: S
authors.lastname: Fukuyama
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nonami
authors.forename: Kouji
authors.initials: K
authors.lastname: Taniguchi
authors.forename: Koichiro
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Takako
authors.initials: T
authors.lastname: Nakano
authors.forename: Miyuki
authors.initials: M
authors.lastname: Tsuda
authors.forename: Mikiko
authors.initials: M
authors.lastname: Matsumura
authors.forename: Masato
authors.initials: M
authors.lastname: Kubo
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Ishikawa
authors.forename: Byoung-gon
authors.initials: BG
authors.lastname: Moon
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takatsu
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakanishi
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshimura
mesh_terms: 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
chemical_list: 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