Expression of mRNA for interleukin-5 in mucosal bronchial biopsies from asthma.

Hamid, Qutayba; Azzawi, May; Sun, Yu; Moqbel, Redwan; Wardlaw, Andrew J.; Corrigan, Christopher; Bradley, Burton; Durham, Stephen R.; Collins, J.V.; Jeffery, Peter K.

doi:10.1172/jci115166

Cited by 804 publications

(368 citation statements)

References 23 publications

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“…Even though we find pronounced production of IL-5 in bone marrow cells, it is clear that IL-5 is produced in several tissue compartments, including the lungs (43)(44)(45)(46). Also, in these experiments, we were able to detect increased levels of IL-5 in both BAL fluid and serum after repeated allergen exposure.…”

Section: Discussionmentioning

confidence: 87%

Eosinophilopoiesis in A Murine Model of Allergic Airway Eosinophilia: Involvement of Bone Marrow IL-5 and IL-5 Receptor α

Tomaki

Zhao

Lundahl

et al. 2000

The Journal of Immunology

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The airway inflammation in asthma is dominated by eosinophils. The aim of this study was to elucidate the contribution of newly produced eosinophils in airway allergic inflammation and to determine mechanisms of any enhanced eosinophilopoiesis. OVA-sensitized BALB/c mice were repeatedly exposed to allergen via airway route. Newly produced cells were identified using a thymidine analog, 5-bromo-2′-deoxyuridine, which is incorporated into DNA during mitosis. Identification of IL-5-producing cells in the bone marrow was performed using FACS. Bone marrow CD3+ cells were enriched to evaluate IL-5-protein release in vitro. Anti-IL-5-treatment (TRFK-5) was given either systemically or directly to the airways. IL-5R-bearing cells were localized by immunocytochemistry. Repeated airway allergen exposure caused prominent airway eosinophilia after three to five exposures, and increased the number of immature eosinophils in the bone marrow. Up to 78% of bronchoalveolar lavage (BAL) granulocytes were 5-bromo-2′-deoxyuridine positive. After three allergen exposures, both CD3+ and non-CD3 cells acquired from the bone marrow expressed and released IL-5-protein. Anti-IL-5 given i.p. inhibited both bone marrow and airway eosinophilia. Intranasal administration of anti-IL-5 also reduced BAL eosinophilia, partly via local effects in the airways. Bone marrow cells, but not BAL eosinophils, displayed stainable amounts of the IL-5R α-chain. We conclude that the bone marrow is activated by airway allergen exposure, and that newly produced eosinophils contribute to a substantial degree to the airway eosinophilia induced by allergen. Airway allergen exposure increases the number of cells expressing IL-5-protein in the bone marrow. The bone marrow, as well as the lung, are possible targets for anti-IL-5-treatment.

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Section: Discussionmentioning

confidence: 87%

Eosinophilopoiesis in A Murine Model of Allergic Airway Eosinophilia: Involvement of Bone Marrow IL-5 and IL-5 Receptor α

Tomaki

Zhao

Lundahl

et al. 2000

The Journal of Immunology

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“…While this upregulation enhances antigen presentation in macrophages, it has been shown that IFN-γ almost completely abrogates the capacity to present antigens by mast cells, central mediators of allergic reactions (Farrar & Schreiber 1993, Frandji et al 1995. Since Th cells can be activated in the airway mucosa, mast cells could act as APCs in the absence of IFN-γ, inducing Th2-type responses through their ability to produce substantial amounts of IL-4 (Hamid et al 1991, Frandji et al 1995, Constant & Bottomly 1997.…”

Section: Ifn-γ γ γ γ γ and Allergic Inflammationmentioning

confidence: 99%

The role of interferon-gamma on immune and allergic responses

Teixeira

Fonseca

Barboza

et al. 2005

Mem. Inst. Oswaldo Cruz

110

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“…Multiple lines of evidence suggest that a chronic, often life-long, Th2-dominated inflammatory response is a cornerstone of the pathogenesis of this disorder (1,(3)(4)(5)(6). There is also a growing appreciation that this inflammation induces structural alterations, including subepithelial fibrosis in the airway, and that this remodeling response may contribute to the generation of asthmatic symptoms and pathophysiology (7).…”

Section: Il-11 Selectively Inhibits Aeroallergen-induced Pulmonarymentioning

confidence: 99%

IL-11 Selectively Inhibits Aeroallergen-Induced Pulmonary Eosinophilia and Th2 Cytokine Production

Wang¹,

Homer²,

Lin³

et al. 2000

The Journal of Immunology

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IL-11 is a pleiotropic cytokine that induces tissue remodeling with subepithelial fibrosis when expressed in the airway. Its effects on the Th2-dominated airway inflammation that is characteristic of asthma, however, are poorly understood. To characterize the effects of IL-11 on Th2 tissue inflammation, we compared the inflammatory responses elicited by OVA in sensitized mice in which IL-11 is overexpressed in a lung-specific fashion (CC10-IL-11) with that in transgene− wild-type littermate controls. Transgene− and CC10-IL-11 transgene+ mice had comparable levels of circulating Ag-specific IgE after sensitization. OVA challenge of sensitized transgene− mice caused airway and parenchymal eosinophilic inflammation, Th2 cell accumulation, and mucus hypersecretion with mucus metaplasia. Exaggerated levels of immunoreactive endothelial cell VCAM-1, mucin (Muc) 5ac gene expression and bronchoalveolar lavage and lung IL-4, IL-5, and IL-13 protein and mRNA were also noted. In contrast, OVA challenge in CC10-IL-11 animals elicited impressively lower levels of tissue and bronchoalveolar lavage inflammation, eosinophilia, and Th2 cell accumulation, and significantly lower levels of VCAM-1 and IL-4, IL-5, and IL-13 mRNA and protein. IL-11 did not cause a comparable decrease in mucus hypersecretion, Muc 5ac gene expression, or the level of expression of RANTES, monocyte chemoattractant protein-2, or monocyte chemoattractant protein-3. In addition, IL-11 did not augment IFN-γ production demonstrating that the inhibitory effects of IL-11 were not due to a shift toward Th1 inflammation. These studies demonstrate that IL-11 selectively inhibits Ag-induced eosinophilia, Th2 inflammation, and VCAM-1 gene expression in pulmonary tissues.

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Expression of mRNA for interleukin-5 in mucosal bronchial biopsies from asthma.

Cited by 804 publications

References 23 publications

Eosinophilopoiesis in A Murine Model of Allergic Airway Eosinophilia: Involvement of Bone Marrow IL-5 and IL-5 Receptor α

Eosinophilopoiesis in A Murine Model of Allergic Airway Eosinophilia: Involvement of Bone Marrow IL-5 and IL-5 Receptor α

The role of interferon-gamma on immune and allergic responses

IL-11 Selectively Inhibits Aeroallergen-Induced Pulmonary Eosinophilia and Th2 Cytokine Production

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