Cytokines in asthma

Chung, Kian Fan; Barnes, Peter J.

doi:10.1136/thx.54.9.825

Cited by 563 publications

(478 citation statements)

References 646 publications

(339 reference statements)

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“…Concerning allergic inflammation in the airways, a number of inflammatory mediators are released not only by mast cells and eosinophils, but also by other mononuclear cells recruited into the airway mucosa (24,25). In this context, different cell types are involved in the amplification of the inflammatory reaction, including neutrophils, fibroblasts, tissue macrophages, and immunocompetent cells (26 -28).…”

Section: Discussionmentioning

confidence: 99%

CD40 on Adult Human Airway Epithelial Cells: Expression and Proinflammatory Effects

Cagnoni

Oddera

Giron‐Michel

et al. 2004

The Journal of Immunology

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CD40/CD40 ligand interaction is an important pathway for B and T cell cooperation and function; functional CD40 molecules have recently been found on nonhematopoietic cells. We detected CD40 in vivo on normal human respiratory epithelial cells and showed that its expression is increased on inflamed airway epithelium. Subsequently, we analyzed its expression and function on primary cultures of human airway epithelial cells. Our data show that CD40 is up-regulated by IFN-β and IFN-γ, its ligation increases the surface expression of CD54 and CD106 and it may stimulate the release of IL-6 and IL-8. The use of Janus kinase 3 (JAK3) and NF-κB inhibitors suggests that both basal and CD40-induced release of the two cytokines is JAK3-dependent. Using colocalization techniques, we revealed the existence of CD40/JAK3 and CD40/TNFR-associated factor 2 interplay. The extent of these interactions may be partial (2–40% of the cells) or massive (80–90% of the cells) in cultured cells. Stimulation via CD40 causes a significant increase in the number of cells expressing colocalization only in the cultures displaying low frequency of initial colocalization. Thus, airway epithelial cells, activated by CD40, may behave as effector cells of the inflammation process and should be considered priority targets for anti-inflammatory therapy. This work identifies CD40 and the correlated JAK3 signaling molecule as potential molecular targets to block the inflammatory functions of epithelial cells.

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Section: Discussionmentioning

confidence: 99%

CD40 on Adult Human Airway Epithelial Cells: Expression and Proinflammatory Effects

Cagnoni

Oddera

Giron‐Michel

et al. 2004

The Journal of Immunology

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“…37 Administration of IFN-g reduced lung Th2 cytokine levels and the degree of allergen-induced AHR with a concomitant reduction in BAL eosinophilia, while administration of an IFN-g-blocking Ab led to an increase in airway CD4 þ T cells and AHR in animal models. 38 Since IFN-g had no effects on lung function, inhalation of IFN-g was has been evaluated as a possible means for preventing toxicity and enhancing the therapeutic effects of IFN-g administration.…”

Section: Il-4 Antagonistic Mutant Dna Inhibits Allergic Airway Inflammentioning

confidence: 97%

A single administration of interleukin-4 antagonistic mutant DNA inhibits allergic airway inflammation in a mouse model of asthma

et al. 2003

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Interleukin 4 (IL-4) is essential for the switching of B cells to IgE antibody production and for the maturation of T helper (Th) cells toward the Th2 phenotype. These mechanisms are thought to play a crucial role in the pathogenesis of the allergic airway inflammation observed in asthma. In the present study, we examined the anti-inflammatory effects of DNA administration of murine IL-4 mutant Q116D/Y119D (IL-4 double mutant, IL-4DM), which binds to the IL-4 receptor a and is an antagonist for IL-4. Immunization of BALB/c mice with alum-adsorbed ovalbumin (OVA) followed by aspiration with aerosolized OVA resulted in the development of allergic airway inflammation. A single administration of IL-4DM DNA before the aerosolized OVA challenge protected the mice from the subsequent induction of allergic airway inflammation. Serum IgE level and extent of eosinophil infiltration in bronchoalveolar lavage (BAL) from IL-4DM DNA-administered mice were significantly lower than those in BAL from control plasmid-immunized mice. In our study, IL-4 or IL-4 mutants were not detected in sera from mice that had received a single administration of IL-4DM DNA. The results of this study provide evidence for the potential utility of IL-4 mutant antagonist DNA inoculation as an approach to gene therapy for asthma.

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“…JNK-1 and JNK-2 have been identified in the lungs of mammals, while JNK-3 has been located to the brain . By phosphorylating these sites, JNKs enhance the transcriptional activity of activation protein (AP)-1, which in turn activates a wide range of immunomodulatory genes (Karin, 1995), which have been implicated in the pathogenesis of chronic asthma (Ip & Davis, 1998;Chung & Barnes, 1999). Increased activation and expression of AP-1 has also been demonstrated in the airways of asthmatics (Demoly et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Allergen‐induced inflammation and airway epithelial and smooth muscle cell proliferation: role of Jun N‐terminal kinase

Eynott

Nath

Leung

et al. 2003

British J Pharmacology

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1 Chronic cellular inflammation and airway wall remodelling with subepithelial fibrosis and airway smooth muscle (ASM) cell hyperplasia are features of chronic asthma. Jun N-terminal kinase (JNK) may be implicated in these processes by regulating the transcriptional activity of activator protein (AP)-1. 2 We examined the effects of an inhibitor of JNK, SP600125 (anthra [1,9-cd] pyrazole-6 (2 H)-one), in a model of chronic allergic inflammation in the rat. 3 Rats sensitised to ovalbumin (OA) were exposed to OA-aerosol every third day on six occasions and were treated with SP600125 (30 mg kg À1 b.i.d; 360 mg in total) for 12 days, starting after the second through to the sixth OA exposure. We measured eosinophilic and T-cell inflammation in the airways, proliferation of ASM cells and epithelial cells by incorporation of bromodeoxyuridine (BrdU), and bronchial responsiveness to acetylcholine. 4 SP600125 significantly reduced the number of eosinophils (Po0.05) and lymphocytes (Po0.05) in bronchoalveolar lavage fluid, suppressed eosinophilic (Po0.05) and CD 2 þ T-cell (Po0.05) infiltration within the bronchial submucosa, and the increased DNA incorporation in ASM (Po0.05) and epithelial cell incorporation (Po0.05). 5 SP600125 did not alter bronchial hyper-responsiveness observed after chronic allergen exposure. 6 Pathways regulated by JNK positively regulate ASM cell proliferation and allergic cellular inflammation following chronic allergen exposure.

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Cytokines in asthma

Cited by 563 publications

References 646 publications

CD40 on Adult Human Airway Epithelial Cells: Expression and Proinflammatory Effects

CD40 on Adult Human Airway Epithelial Cells: Expression and Proinflammatory Effects

A single administration of interleukin-4 antagonistic mutant DNA inhibits allergic airway inflammation in a mouse model of asthma

Allergen‐induced inflammation and airway epithelial and smooth muscle cell proliferation: role of Jun N‐terminal kinase

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