Expression of the IL-4 receptor α-subunit is increased in bronchial biopsy specimens from atopic and nonatopic asthmatic subjects☆☆☆★★★

Kotsimbos, T.; Ghaffar, Omar; Minshall, Eleanor; Humbert, Marc; Durham, Stephen R.; Pfister, R; Menz, Günter; Kay, A. B.; Hamid, Qutayba

doi:10.1016/s0091-6749(98)70029-6

Cited by 75 publications

(40 citation statements)

References 33 publications

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“…In humans, it has been shown that expression of IL-4 and its receptor correlates with asthma [24,25]. Furthermore, murine studies demonstrate a role for IL-4 in BAL and lung eosinophil accumulation [26,27], and mice deficient in IL-4 are not hyperreactive when sensitized and challenged to OVA [28].…”

Section: Discussionmentioning

confidence: 99%

CD8+ T cell contributions to allergen induced pulmonary inflammation and airway hyperreactivity

et al. 2005

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The pathogenesis of asthma has been linked to the production of type 2 cytokines, which can be expressed by several cell types in the lung. These studies investigated CD8 + T cell responses in a murine cockroach antigen (CRA) model of asthma. The results from these present studies show that depletion of CD8 + T cells after allergen sensitization to CRA significantly reduces airway hyperreactivity, airway eosinophilia and pulmonary type 2 cytokine levels. The data demonstrate that CD8 + T cells from CRA-sensitized mice can produce type 2 cytokines IL-4, IL-5 and IL-13 upon antigen challenge, and that the transfer of these cells into naive mice will cause airway hyperreactivity when exposed to CRA. We found that the transferred airway response is dependent on both IL-4 and IL-13 from CD8 + T cells using cytokine knockout mice. Compared to CD4 + T cells, CD8 + T cells were not as numerous in the lungs of sensitized and challenged mice, but were as efficacious in the transfer of airway disease. The most severe airway response was observed when both CD4 + and CD8 + T cells were transferred at the same time. Altogether, these studies highlight a role for CD8 + T lymphocytes in the development of allergen-induced airway responses.

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Section: Discussionmentioning

confidence: 99%

CD8+ T cell contributions to allergen induced pulmonary inflammation and airway hyperreactivity

et al. 2005

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“…It is reasonable to hypothesize that a similar scenario may apply to the lung. It has been suggested that bronchial biopsies from atopic asthmatics compared with atopic control subjects exhibit increased expression of IL-4␣ mRNA and protein in the epithelium, subepithelium, and EC layer (31). There is evidence that Th2 cytokines (IL-4 and IL-13) induce VEGF from human airway smooth muscle cells (SMCs) (24,25).…”

Section: Il-4 Is Proangiogenic In the Lungmentioning

confidence: 99%

IL-4 Is Proangiogenic in the Lung under Hypoxic Conditions

Yamaji-Kegan

Angelini

et al. 2009

The Journal of Immunology

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IL-4-mediated proangiogenic and proinflammatory vascular responses have been implicated in the pathogenesis of chronic lung diseases such as asthma. Although it is well known that hypoxia induces pulmonary angiogenesis and vascular alterations, the underlying mechanism of IL-4 on the pulmonary vasculature under hypoxic conditions remains unknown. In this context, we designed the present study to determine the functional importance of IL-4 for pulmonary angiogenesis under hypoxic conditions using IL-4 knockout (KO) animals. Our results show that hypoxia significantly increased IL-4Rα expression in wild-type (WT) control lungs. Even though hypoxia significantly up-regulated vascular endothelial growth factor (VEGF) receptor expression in the lungs of both genotypes, hypoxia-induced VEGF, VCAM-1, HIF-1α, and ERK phosphorylation were significantly diminished in IL-4 KO lungs as compared with WT control lungs. In addition, hypoxia-induced pulmonary angiogenesis and proliferating activities in the airway and pulmonary artery were significantly suppressed in IL-4 KO lungs as compared with WT control lungs. We also isolated primary lung fibroblasts from these genotypes and stimulated these cells with hypoxia. Hypoxia-induced VEGF production was significantly suppressed in lung fibroblasts from IL-4 KO mice. These in vitro results are in accordance with the in vivo data. Furthermore, we observed a significant increase of hypoxia-induced pulmonary angiogenesis in STAT6 KO mice similar to that in WT controls. In conclusion, IL-4 has proangiogenic properties in the lung under hypoxic conditions via the VEGF pathway, and this is independent of the STAT6 pathway.

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“…The IL-4R is a heterodimer, consisting of the IL-4-binding IL4Ra chain and a second chain, which is either the cc chain (shared in common with the receptor for IL-2, -7, -9 and -15) or the IL-13Ra chain [11,12]. Increased expression of the IL-4Ra chain in the epithelium and subepithelium of asthmatic airways has been reported [13]. Polymorphisms of the IL-4 and IL-4Ra genes have also been related to asthma severity.…”

Section: Interleukin-4mentioning

confidence: 99%

Cytokines in asthma

Kips

2001

European Respiratory Journal

165

107

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The airway inflammation underlying asthma is regulated by a network of mutually interacting cytokines. The exact functional role of each individual cytokine in the pathogenesis of the disease remains to be fully established.Type 2 T-helper cells are currently considered to play a crucial role in this process. In vivo animal data suggest a sequential involvement of interleukin (IL)-4 and IL-5 in the induction of allergen-induced airway changes. The potential role of other type 2 T-helper cell-like cytokines in asthma is increasingly being recognized. In particular, IL-4 and -13 display a large degree of redundancy. Whereas IL-4 seems to be crucial in the primary allergen sensitization process, IL-13 might be more important during secondary exposure to aerosolized allergen. Animal models also indicate that T-cellderived cytokine production, rather than eosinophil influx or immunoglobulin-E synthesis, is causally related to altered airway behaviour.An important aspect when evaluating the functional role of cytokines in a complex disease such as asthma is the interaction with other cytokines in the microenvironment. Increased expression of pro-inflammatory cytokines such as tumour necrosis factor-a can further enhance the inflammatory process, and is increasingly linked to disease severity. In addition, decreased expression of immunoregulatory cytokines, including interleukin-12, interleukin-18 or interferon gamma could also strengthen the type 2 T-helper cell-driven inflammatory process.

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Expression of the IL-4 receptor α-subunit is increased in bronchial biopsy specimens from atopic and nonatopic asthmatic subjects☆☆☆★★★

Cited by 75 publications

References 33 publications

CD8+ T cell contributions to allergen induced pulmonary inflammation and airway hyperreactivity

CD8+ T cell contributions to allergen induced pulmonary inflammation and airway hyperreactivity

IL-4 Is Proangiogenic in the Lung under Hypoxic Conditions

Cytokines in asthma

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