Effects of Rho‐kinase inactivation on eosinophilia and hyper‐reactivity in murine airways by allergen challenges

Taki, Fumio; Kumakura, Hiroaki; Kobayashi, Takashi; Ohta, Hiroyuki; Aratake, H.; Shimokata, Kaoru

doi:10.1111/j.1365-2222.2007.02693.x

Cited by 61 publications

(88 citation statements)

References 36 publications

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“…This may be particularly important as there is considerable interest in pharmacological modulation of the RhoA pathway in allergic disease and asthma. For example, the ROCK inhibitor, Y-27632, has been investigated in animal models as a modulator of eosinophilia and airway hyperresponsiveness (51,52). Because we shown in human eosinophils that use of the Rho/ROCK pathway is cell context and environment context-dependent, this has important implications for the development of drugs targeting the migration of these cells within human tissue.…”

Section: Discussionmentioning

confidence: 98%

CCL11 and GM-CSF Differentially Use the Rho GTPase Pathway to Regulate Motility of Human Eosinophils in a Three-Dimensional Microenvironment

Muessel

Scott

Friedl

et al. 2008

The Journal of Immunology

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Asthma is a common disease that causes considerable morbidity. Increased numbers of airway eosinophils are a hallmark of asthma. Mechanisms controlling the entry of eosinophils into asthmatic lung have been intensively investigated, but factors regulating migration within the tissue microenvironment are less well understood. We modeled this by studying chemoattractant and growth factor-mediated human eosinophil migration within a three-dimensional collagen matrix. Stimulation with GM-CSF induced dose-dependent, random migration with a maximum of 77 ± 4.7% of cells migrating. In contrast, CCL11 and C5a caused a more modest although significant degree of migration (19 ± 1.8% and 20 ± 2.6%, respectively). Migration to GM-CSF was partially dependent on Ca2+ and αΜβ2 integrins. The Rho family of small GTPases regulates intracellular signaling of cell migration. GM-CSF-induced migration was only partially dependent on Rho kinase/Rho-associated kinase (ROCK) and was independent of RhoA activation. In contrast, CCL11-induced migration was fully dependent on both RhoA and ROCK. Activation of RhoA was therefore neither necessary nor sufficient to cause eosinophil migration in a three-dimensional collagen environment. This study suggests that eosinophil growth factors are likely to be required for eosinophil migration within the bronchial mucosa, and this involves signal transduction pathways distinct from those used by G protein-associated chemoattractants.

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Section: Discussionmentioning

confidence: 98%

CCL11 and GM-CSF Differentially Use the Rho GTPase Pathway to Regulate Motility of Human Eosinophils in a Three-Dimensional Microenvironment

Muessel

Scott

Friedl

et al. 2008

The Journal of Immunology

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“…They were then placed in an acrylic chamber and challenged with 1% OVA for 10 min daily by a nebulizer (IS-2; Paris, Starnberg, Germany) between days 21 and 25. 10) Saline was used in place of OVA during the sensitisation and challenge stages of the protocol as a negative control. All protocols described in this study were approved by the Animal Ethics Committee of Nagoya University Graduate School of Medicine, Nagoya, Japan.…”

Section: Sensitisation and Challenge With Ovalbuminmentioning

confidence: 99%

Thalidomide Attenuates Airway Hyperresponsiveness and Eosinophilic Inflammation in a Murine Model of Allergic Asthma

Asano

Kumakura

Taki

et al. 2010

Biological & Pharmaceutical Bulletin

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Bronchial asthma has clinical manifestations, which include variable degrees of airflow obstruction, airway hyperresponsiveness, and airway inflammation.1) The inflammatory process in asthma is dominated by T helper-2 (Th2) cells which produce interleukin-4 (IL-4), IL-5, and IL-13. 2)Thalidomide was synthesized in 1954 by CIBA Pharmaceutical Company, and prescribed as a sedative, tranquiliser, and antiemetic for morning sickness. Because the highest risk for teratogenicity arose when the drug was taken between weeks 3 and 8 after conception, it was withdrawn from many countries including Japan. However, the drug was revived as an effective treatment for erythema nodosum leprosum lesions in 1965. The U.S.A. Food and Drug Administration approved it for this indication in 1998. 3)Thalidomide, which is metabolized by cytochrome P450, 3,4) has a wide range of pharmaceutical and biological activities. Currently, clinical investigations of thalidomide have been conducted in patients with diverse diseases, including multiple myeloma, rheumatoid arthritis, and human immunodeficiency virus infection. 5,6) The beneficial pharmacological effects elicited by thalidomide include anti-angiogenic, anti-viral, anti-inflammatory, and immunomodulatory activities, 5,7) although the precise mechanisms are unknown.8)It has been reported that thalidomide administered with albendazole suppressed eosinophilic infiltration in cerebrospinal fluid in a murine vermination model. 9) However, little is known about the effect of thalidomide on the airway hyperresponsiveness and eosinophilic inflammation in allergic asthma.The purpose of this study was to investigate the effects of thalidomide on airway inflammation and hyperresponsiveness in a murine model of allergic asthma. We hypothesized that thalidomide would have anti-inflammatory effects in allergic asthma. MATERIALS AND METHODS Sensitisation and Challenge with OvalbuminSevenweek-old female BALB/c mice (SLC, Shizuoka) were purchased and maintained in our specific pathogen-free animal facility. The mice were maintained at room temperature (23Ϯ2°C) and humidity (55Ϯ10%) in an air-conditioned room. They were fed a standard laboratory diet and given water ad libitum. They were sensitised by an intraperitoneal injection with 100 mg ovalbumin (OVA) and 1 mg alum in 200 ml of phosphate-buffered saline (PBS) on day 0, and then by a hypodermic injection with 10 mg OVA in 20 ml of PBS on day 14. They were then placed in an acrylic chamber and challenged with 1% OVA for 10 min daily by a nebulizer (IS-2; Paris, Starnberg, Germany) between days 21 and 25. 10)Saline was used in place of OVA during the sensitisation and challenge stages of the protocol as a negative control. All protocols described in this study were approved by the Animal Ethics Committee of Nagoya University Graduate School of Medicine, Nagoya, Japan.Treatment Protocols For in vivo animal experiments, thalidomide (30, 100, or 300 mg/kg) was suspended in 0.5% carboxymethylcellulose, vortexed for 5 min, and administered orally via a ...

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“…Para todas estas atividades a proteína Rho possui uma proteína efetora denominada Rho-quinase (Fukata et al, 2001;Henry et al, 2005;Taki et al, 2007).…”

Section: Inibição Da Rho-quinaseunclassified

Efeitos dos inibidores de NF Kappa-B e Rho Quinase em um modelo de asma animal: comparação com o tratamento com corticosteroides

Souza¹

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Effects of Rho‐kinase inactivation on eosinophilia and hyper‐reactivity in murine airways by allergen challenges

Cited by 61 publications

References 36 publications

CCL11 and GM-CSF Differentially Use the Rho GTPase Pathway to Regulate Motility of Human Eosinophils in a Three-Dimensional Microenvironment

CCL11 and GM-CSF Differentially Use the Rho GTPase Pathway to Regulate Motility of Human Eosinophils in a Three-Dimensional Microenvironment

Thalidomide Attenuates Airway Hyperresponsiveness and Eosinophilic Inflammation in a Murine Model of Allergic Asthma

Efeitos dos inibidores de NF Kappa-B e Rho Quinase em um modelo de asma animal: comparação com o tratamento com corticosteroides

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