Immune Netw.  2007 Mar;7(1):18-25. 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

• Lee YM
• Kang NI
• Lee HK

• KMID: 2150623
• DOI: http://doi.org/10.4110/in.2007.7.1.18

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.

Keyword

Asthma; steroid; NF-kappaB; CXC chemokine; neutrophilia

MeSH Terms

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
Chemokines, CC
Chemokines, CXC
Cytokines
Dexamethasone
Glucocorticoids
Mucins
NF-kappa B
Tumor Necrosis Factor-alpha