Dexamethasone Does Not Inhibit Airway CXC Chemokine Expression and Neutrophilia in a Murine Model of Asthma - Mechanism of Steroid Resistance in Asthma.
- Author:
Young Man LEE
1
;
Nam In KANG
;
Hern Ku LEE
Author Information
- Publication Type:Original Article
- Keywords: Asthma; steroid; NF-kappaB; CXC chemokine; neutrophilia
- MeSH: Animals; Asthma*; Bronchoalveolar Lavage; Chemokines, CC; Chemokines, CXC; Cytokines; Dexamethasone*; Eosinophilia; Glucocorticoids; Humans; Immunization; Lung; Mice; Monocytes; Mucins; NF-kappa B; Ovum; Phenotype; Tumor Necrosis Factor-alpha
- From:Immune Network 2007;7(1):18-25
- CountryRepublic of Korea
- Language:English
- 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-kappaB activation in asthmatic lungs, and also inhibited bronchoalveolar lavage (BAL) levels of NF-kappaB-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.
