KMID : 0923620070070010018
|
|
Immune Network 2007 Volume.7 No. 1 p.18 ~ p.25
|
|
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 Kang Nam-In Lee Hern-Ku
|
|
Abstract
|
|
|
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-¥êB activation in asthmatic lungs, and also inhibited bronchoalveolar lavage (BAL) levels of NF-¥êB-dependent cytokines such as TNF-¥á 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. (Immune Network 2007;7(1):18-25)
|
|
KEYWORD
|
|
Asthma, steroid, NF-¥êB, CXC chemokine, neutrophilia
|
|
FullTexts / Linksout information
|
|
|
|
Listed journal information
|
|
|
|