Antiinflammatory Effects of Genistein, a Tyrosine Kinase Inhibitor, on a Guinea Pig Model of Asthma

Duan, Wei; Kuo, I-Chun; Selvarajan, Sathiyamoorthy; Chua, Kaw Yan; Bay, Boon Huat; Wong, W.S. Fred

doi:10.1164/rccm.200205-420oc

Cited by 114 publications

(79 citation statements)

References 38 publications

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“…genesis, the possible therapeutic use of a tyrosine kinase inhibitor to treat asthma has been investigated in several studies (Duan et al, 2003Vargaftig and Singer, 2003). Until now other studies have showed that EGFR tyrosine kinase inhibitors have anti-inflammatory effects in asthma model, but can not explain adequate mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Potential use of an anticancer drug gefinitib, an EGFR inhibitor, on allergic airway inflammation

Hur

Lee²,

Lee³

et al. 2007

Exp Mol Med

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The EGFR plays an essential role in goblet cell hyperplasia and mucus hypersecretion. EGFR has an intrinsic tyrosine kinase activity that, when activated, induces the production of MUC5AC through the signaling kinase cascade in the airway epithelium. We have investigated the effects of an EGFR tyrosine kinase inhibitor, gefitinib, on ovalbumin (OVA)-induced, allergic inflammation in airway epithelia of mice. OVA-sensitized mice were pretreated with gefitinib at two different doses (12.5 and 50 mg/kg) and then challenged with OVA. The OVA challenge increased the total cell count and eosinophil count in bronchoalveolar lavage fluid (BALF), as well as the concentrations of T-helper2 (Th2) cytokines, such as IL-4 and IL-13, overall eosinophil recruitment in the lung tissue and airway hyperresponsiveness (AHR). Pretreatment with gefitinib reduced the inflammatory cell counts and released cytokine concentrations (IL-4 and IL-13) in BALF, as well as eosinophil recruitment in the lungs and AHR, in a dose-dependent manner. This was associated with decreased EGFR and Akt phosphorylation. We showed that gefitnib inhibits EGFR and phosphoinositol 3'-kinase (PI3K)/Akt activation which were activated in OVA sensitized mice. These findings suggest that inhibitors of the EGFR cascade may have a role in the treatment of asthma.

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Section: Discussionmentioning

confidence: 99%

Potential use of an anticancer drug gefinitib, an EGFR inhibitor, on allergic airway inflammation

Hur

Lee²,

Lee³

et al. 2007

Exp Mol Med

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“…Considered a broad-spectrum protein tyrosine kinase inhibitor, genistein (42) (15 mg/kg administered intraperitoneally to sensitized male Hartley guinea pigs) inhibited ovalbumin-induced acute bronchoconstriction and airway hyperresponsiveness to methacholine, eosinophilic inflammation both in BALF and in airways and eosinophil peroxidase activity in cell-free assays. The authors suggested that the inhibition of the tyrosine signaling cascade by via genistein (42) stimulus may present a therapeutic possibility for allergic airway diseases [122].…”

Section: Asthmamentioning

confidence: 99%

Structure-Activity Association of Flavonoids in Lung Diseases

et al. 2014

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Flavonoids are polyphenolic compounds classified into flavonols, flavones, flavanones, isoflavones, catechins, anthocyanidins, and chalcones according to their chemical structures. They are abundantly found in Nature and over 8,000 flavonoids have from different sources, mainly plant materials, have been described. Recently reports have shown the valuable effects of flavonoids as antiviral, anti-allergic, antiplatelet, antitumor, antioxidant, and anti-inflammatory agents and interest in these compounds has been increasing since they can be helpful to human health. Several mechanisms of action are involved in the biological properties of flavonoids such as free radical scavenging, transition metal ion chelation, activation of survival genes and signaling pathways, regulation of mitochondrial function and modulation of inflammatory responses. The anti-inflammatory effects of flavonoids have been described in a number of studies in the literature, but not frequently associated to respiratory disease. Thus, this review aims to discuss the effects of different flavonoids in the control of lung inflammation in some disorders such as asthma, lung emphysema and acute respiratory distress syndrome and the possible mechanisms of action, as well as establish some structure-activity relationships between this biological potential and chemical profile of these compounds.

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“…In mice, injection of genistein caused a decrease in relative percentages of both thymic CD4(+)CD8()) and CD4(+)CD8(+) thymocytes (39,45). As genistein is an inhibitor of tyrosine kinase -an enzyme playing a pivotal role in the activation of inflammatory cells, it has been proposed that soy isoflavones have immunosuppressive and antiinflammatory properties (78)(79)(80). However, a few experimental data does not correspond with this assumption.…”

Section: Phytoestrogens Gender and Allergic Responsementioning

confidence: 99%

“…Daidzein exerted a stimulatory effect on nonspecific immunity, as shown by enhancement in the phagocytic response of peritoneal mice macrophages and thymus weight (43). Studies on an guinea-pig model of asthma demonstrated that genistein, contrary to daidzein, which has no inhibitory activity against tyrosine kinases, effectively reduced acute bronchoconstriction, pulmonary eosinophilia, and AHR induced by ovalbumine (OVA), but not histamine or metacholine (79). However, other results show that the reduction of antigen-induced eosinophilia in the lung of the asthmatic guinea-pigs being on a diet enriched with isoflavones is accompanied by a potentially detrimental increase in antigen-induced leakage of protein into the airspace (78).…”

Section: Phytoestrogens Gender and Allergic Responsementioning

confidence: 99%

Endocrine disrupters – potential modulators of the immune system and allergic response

Chałubiński¹,

Kowalski²

2006

Allergy

150

103

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Endocrine disrupters (EDs) are environmental pollutants of industrial or agricultural origin (e.g. herbicides, fungicides, insecticides, industrial chemicals) that may influence health of wildlife and human. Endocrine‐disrupting effect is obtained by mimicking the action of the steroid hormones and has been associated with several reproductive disorders as well as cancerogenesis both in animals and humans. EDs can also influence synthesis of cytokines, immunoglobulins, and cell mediators as well as immune cell activation and survival. Modulation by EDs of interleukin‐4 production, Th1/Th2 balance and IgE production suggest their potential effect on allergic immune responses. The aim of this review was to summarize data indicating a potential effect of EDs exposure on the immune system and allergic responses.

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Antiinflammatory Effects of Genistein, a Tyrosine Kinase Inhibitor, on a Guinea Pig Model of Asthma

Cited by 114 publications

References 38 publications

Potential use of an anticancer drug gefinitib, an EGFR inhibitor, on allergic airway inflammation

Potential use of an anticancer drug gefinitib, an EGFR inhibitor, on allergic airway inflammation

Structure-Activity Association of Flavonoids in Lung Diseases

Endocrine disrupters – potential modulators of the immune system and allergic response

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