Elevated expression of messenger ribonucleic acid encoding IL-13 in the bronchial mucosa of atopic and nonatopic subjects with asthma

Humbert, Marc; Durham, Stephen R.; Kimmitt, P.T.; Powell, Nick; Assoufi, B; Pfister, R; Menz, Günter; Kay, A. B.; Corrigan, Chris J.

doi:10.1016/s0091-6749(97)70028-9

Cited by 294 publications

(171 citation statements)

References 25 publications

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“…IL-13 and the Th2 system are recognized as a key mediator in the pathogenesis of bronchial asthma 45,46 and its mechanism of action and means of control are of interest as new therapeutic targets. 47 IL-13 mRNA and protein are expressed in the lungs of allergen-challenged human volunteers 48 and asthma patients, 49 and its effect appears to be mediated via elevating the expression of MHC class-II and CD40 on CD11c-high alveolar DCs. 50 In experimental asthma models, airway hyperreactivity accompanied by high levels of IL-4 and IL-5 secretion can be induced in intact but not IL-13À/À mice.…”

Section: Discussionmentioning

confidence: 99%

“…51,52 Sensitized animals can be protected by treatment with IL-13Ra-chain constructs, 53 and although the IL-4Ra-chain may be involved, this is disputed. 46,49 Mice whose Th1 system is crippled by the genetic disruption of T-bet expression develop spontaneous asthma-like disease, which is accompanied by high numbers of CD44 and CD69 bright CD4 þ T cells; again, this condition can be ameliorated by the direct blockade of IL-13. 54 In humans, allergen-specific T-cell clones produce IL-13, 55 and IL-13 will elevate mast-cell proliferation; 56 experimental anti-Th2 strategies which do not address IL-13 have failed.…”

Section: Discussionmentioning

confidence: 99%

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Human interferon lambda-1 (IFN-λ1/IL-29) modulates the Th1/Th2 response

et al. 2007

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Interferon lambda-1 (IFN-l1/IL-29) is a member of the Type-III interferon family, which contains three ligands: IFN-l1, 2 and 3. These three ligands use the same unique heterodimeric receptor composed of CRF2-12 (IFN-l-R1/IL-28Ra) and CRF2-4 (IL10-R-b) chains. Like their close relatives, the Type-I interferons, IFN-l1, 2 and 3, promote the phosphorylation of STAT1 and STAT2, induce the ISRE3 complex, elevate OAS and MxA expression and exhibit antiviral activity in vitro. Their use of the IL10-R-b chain and their ability to phosphorylate STAT3, STAT4 and STAT5 suggested that they may also exhibit immunomodulatory activity; their antiviral action led us to hypothesize that this activity might be directed toward the Th1/Th2 system. Here, we have demonstrated that IFN-l1 altered the activity of Th cells in three separate experimental systems: (i) mitogen stimulation, (ii) mixed-lymphocyte reaction (MLR) and (iii) stimulation of naive T cells by monocyte-derived dendritic cells (mDC). In Con-A stimulation assays, the inclusion of IFN-l1 consistently led to markedly diminished levels of secreted interleukin (IL-13) with occasional coincident, modest elevation of secreted IFN-g. IL-13 secretion was 100-fold more sensitive to IFN-l1 than was IFN-g secretion. These observations were also made in the allogeneic two-way MLR. IFN-l1 was able to alter cytokine-mediated Th biasing and when naive T cells were exposed to allogeneic mDC that had been matured in the presence of IFN-l1, secreted IL-13 was again markedly and consistently reduced, whereas secreted IFN-g was largely unaltered. These functions were independent of IL-10. Our data support a hitherto unsuspected role for IFN-l1 in modulating the development of Th1 and Th2 cells, with an apparent emphasis on the diminution of IL-13 secretion.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Human interferon lambda-1 (IFN-λ1/IL-29) modulates the Th1/Th2 response

et al. 2007

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“…11,18,[28][29][30][31] This discovery emphasizes the uniqueness of epithelia-derived IL-19 in allergic diseases and suggests important roles for IL-13 and IL-17A in IL-19 regulation. [32][33][34] We hypothesize that airway epithelial IL-19 is induced by IL-17A and T H 2 cytokines, mainly IL-13, to further potentiate a T H 2-dominant response in a positive feedback manner in the context of allergic airway diseases, such as asthma.…”

Section: Discussionmentioning

confidence: 99%

“…In allergic asthma IL-4 and IL-13 are central mediators of many pathologic responses, such as airway hyperreactivity, mucous cell hyperplasia, and eosinophil recruitment. [32][33][34][35][36] IL-17A also plays a role in human asthmatic patients and in airways of allergic animals. 18,28,30,[37][38][39] Studies have found that in patients with moderate-to-severe asthma, neutrophils are found to be more abundant than eosinophils in the bronchoalveolar lavage fluid.…”

Section: Discussionmentioning

confidence: 99%

Potentiation of IL-19 expression in airway epithelia by IL-17A and IL-4/IL-13: Important implications in asthma

Huang

Wachi

Thai

et al. 2008

Journal of Allergy and Clinical Immunology

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“…Eosinophil recruitment to sites of allergic inflammation depends on the concerted action of a variety of molecules, including chemokines, and activation of PI3K (Sotsios and Ward, 2000). IL-4 and IL-13 are chemotactic for eosinophils, which are principal elements in the pathogenesis of allergic inflammation (Rankin et al, 1996;Humbert et al, 1997). Eosinophil transmigration into the airways is a complex process that is coordinated by Th2 cytokines and several adhesion molecules (Lukacs, 2001).…”

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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Elevated expression of messenger ribonucleic acid encoding IL-13 in the bronchial mucosa of atopic and nonatopic subjects with asthma

Cited by 294 publications

References 25 publications

Human interferon lambda-1 (IFN-λ1/IL-29) modulates the Th1/Th2 response

Human interferon lambda-1 (IFN-λ1/IL-29) modulates the Th1/Th2 response

Potentiation of IL-19 expression in airway epithelia by IL-17A and IL-4/IL-13: Important implications in asthma

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

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