[논문]Dexamethasone Does Not Inhibit Airway CXC Chemokine Expression and Neutrophilia in a Murine Model of Asthma - Mechanism of Steroid Resistance in Asthma

Lee, Young-Man; Kang, Nam-In; Lee, Hern-Ku

doi:10.4110/in.2007.7.1.18

Dexamethasone Does Not Inhibit Airway CXC Chemokine Expression and Neutrophilia in a Murine Model of Asthma - Mechanism of Steroid Resistance in Asthma 원문보기

Immune network : official journal of the Korean association of immunobiologists, v.7 no.1, 2007년, pp.18 - 25

Lee, Young-Man (Department of Immunology, Chonbuk National University Medical School) , Kang, Nam-In (Department of Immunology, Chonbuk National University Medical School) , Lee, Hern-Ku (Department of Immunology, Chonbuk National University Medical School)

Abstract ▼ AI-Helper

Background: Although glucocorticoids (GCs) are effective in controlling asthma in the majority of patients, a subset of asthmatics fails to demonstrate a satisfactory response, even to systemic GC therapy. This population is referred to as being "steroid-resistant". The actual mechanism underlying steroid resistance in asthma remains to be elucidated. Methods: We have investigated how dexamethasone (DEX) regulates asthmatic phenotypes in a murine model of asthma, in which mice received i.p. immunization twice, followed by two bronchoprovocations with aerosolized OVA with a one-week interval, which we have recently described. Results: Pretreatment with DEX resulted in an inhibition of NF-${\kappa}B$ activation in asthmatic lungs, and also inhibited bronchoalveolar lavage (BAL) levels of NF-${\kappa}B$-dependent cytokines such as TNF-${\alpha}$ and CC chemokines [eotaxin and monocyte chemotactic protein (MCP)-1]. DEX was effective in suppressing airway hyperresponsiveness (AHR) at 10 h, Th2-dependent asthmatic phenotypes such as airway eosinophilia, BAL levels of Th2 cytokines (IL-5 and IL-13), and mucin production. However, DEX failed to suppress BAL levels of CXC chemokines [macrophage inflammatory protein-2 (MIP-2) and keratinocyte-derived chemokine (KC)] and airway neutrophilia. Conclusion: Airway neutrophilia is among the phenomena observed in patients with severe GC-resistant asthma. This study will provide insight into the molecular basis for airway neutrophila seen in steroid-resistant asthma. Further studies are required to delineate the underlying mechanism of CXC chemokine expression in asthma.

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제안 방법

In this study, we investigated the manner by which DEX regulates IgG-IC-induced NF- k B activation and NF- A:B-dependent asthmatic phenotypes. We found that DEX suppressed NF- /rB activation, and also suppressed subsequent BAL fluid levels of TNF- a TNF-(2-induced late AHR, eotaxin, and MCP-1.
The effect of DEX on Th2 cell-mediated asthmatic phenotypes such as airway eosinophilia, BAL levels of Th2 cytokines (IL-5 and IL-13), and airway mucus production were examined. OVA-immunized and -challenged animals showed significant increases in the numbers of BAL eosinophils at 48 h after the second OVA challenge compared with saline-challenged controls (Fig.

데이터처리

Data were expressed as mean 士 SD. Statistical comparison was performed using one-way ANOVA followed by the Fisher test. Significant differences between the groups were determined using the unpaired Students /-test.

이론/모형

Statistical comparison was performed using one-way ANOVA followed by the Fisher test. Significant differences between the groups were determined using the unpaired Students /-test. A value of p< 0.

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