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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   (Department of Immunology, Chonbuk National University Medical SchoolUU0001120  ); Kang, Nam-In   (Department of Immunology, Chonbuk National University Medical SchoolUU0001120  ); Lee, Hern-Ku   (Department of Immunology, Chonbuk National University Medical SchoolUU0001120  );
  • 초록

    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.

  • 주제어

    Asthma .   steroid .   NF- ${\kappa}B$ .   CXC chemokine .   neutrophilia.  

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