Korean J Asthma Allergy Clin Immunol.  2006 Jun;26(2):136-144.

Subepithelial Fibrosis-associated Mediators in Mice with Chronic Asthma: Effects of CpG-oligodeoxynucleotides on TGF-beta1 and IL-17

Abstract

BACKGROUND: Important features of airway remodeling in asthma include the formation of subepithelial fibrosis and increased deposition of collagen. Profibrotic cytokines such as TGF-beta1 and IL-17 are involved in the formation of subepithelial fibrosis and are increased in patients with asthma, particularly in these severe disease. Previous reports have represented that administration of CpG-oligodeoxynucleotides (CpG-ODN) before allergen sensitization or challenge inhibits chronic inflammation and remodeling of airway in mice with chronic asthma, but the effect of CpG- ODN on TGF-beta1 and IL-17 have not been evaluated.
OBJECTIVE
To evaluate the effect of CpG-ODN on the expression of these profibrotic cytokines and on collagen deposition, this study was performed in mice with chronic asthma. METHOD: Mice were subjected to repetitive ovalbumin (OVA) challenge for 2 months. CpG-ODN was administered intraperitoneally for sensitization. After the final challenge, airway hyperresponsiveness, peribronchial fibrosis, and levels of lung hydroxyproline were assessed. Levels of TGF-beta1 and IL-17 in bronchoaveolar lavage (BAL) were assessed by ELISA and the number of TGF-beta1+cells and IL-17+cells in peribronchial area by immumohistochemistry. RESULT: CpG-ODN significantly reduced airway hyperresponsiveness, eosinophil infiltration, and peribronchial fibrosis. Levels of TGF-beta1 in BAL fluid (353+/-94 vs 270+/-66 pg/mL, OVA vs OVA+CpG, P<0.05) and peribronchial TGF-beta1+cells (46+/-10 vs 27+/-5 TGF-beta1+ cells/bronchus, OVA vs OVA+CpG, P<0.01) were significantly reduced in mice treated with CpG-ODN. Levels of IL-17 in BAL fluid (62+/-30 vs 34+/-10 pg/mL, OVA vs OVA+CpG, P=0.074) were not significantly reduced, but peribronchial IL-17+cells (27+/-7 vs 7.5+/-5.3 IL-17+ cells/bronchus, OVA vs OVA+CpG, P<0.01) and levels of lung hydroxyproline (13.1+/-5.3 vs 9.1+/-2.71microgram/mL, OVA vs OVA+CpG, P<0.01) were significantly reduced in mice treated with CpG-ODN.
CONCLUSION
CpG-ODN significantly reduced the levels of allergen-induced peribronchial fibrosis and collagen deposition. The reduction in peribronchial fibrosis and collagen deposition mediated by CpG-ODN might be due to several mechanisms including inhibition of profibrotic cytokines of TGF-beta1 and IL-17 and a reduction in the number of peribronchial inflammatory cells expressing TGF-beta1.

MeSH Terms

Airway Remodeling
Animals
Asthma*
Collagen
Cytokines
Enzyme-Linked Immunosorbent Assay
Eosinophils
Fibrosis
Humans
Hydroxyproline
Inflammation
Interleukin-17*
Lung
Mice*
Ovalbumin
Ovum
Therapeutic Irrigation
Transforming Growth Factor beta1*
Collagen
Cytokines
Hydroxyproline
Interleukin-17
Ovalbumin
Transforming Growth Factor beta1