CpG oligodeoxynucleotides can reverse Th2-associated allergic airway responses and alter the B7.1/B7.2 expression in a murine model of asthma.
CpG oligodeoxynucleotides (CpG-ODN) administered during Ag sensitization or before Ag challenge can inhibit allergic pulmonary inflammation and airway hyperreactivity in murine models of asthma. In this study, we investigated whether CpG-ODN can reverse an ongoing allergic pulmonary reaction in a mouse model of asthma. AKR mice were sensitized with conalbumin followed by two intratracheal challenges at weekly intervals. CpG-ODN was administered 24 h after the first Ag challenge. CpG-ODN administration reduced Ag-specific IgE levels, bronchoalveolar lavage fluid eosinophils, mucus production, and airway hyperreactivity. We found that postchallenge CpG-ODN treatment significantly increased IFN-gamma concentrations and decreased IL-13, IL-4, and IL-5 concentrations in bronchoalveolar lavage fluids and spleen cell culture supernatants. Postchallenge CpG-ODN treatment also increased B7.1 mRNA expression and decreased B7.2 mRNA expression in lung tissues. These results suggest that CpG-ODN may have potential for treatment of allergic asthma by suppressing Th2 responses during IgE-dependent allergic airway reactions. The down-regulation of Th2 responses by CPG-ODN may be associated with regulation of the costimulatory factors B7.1 and B7.2.
Serebrisky
D
D
Department of Pediatrics, Mount Sinai School of Medicine, New York, NY 10029, USA.
Teper
A A
AA
Huang
C K
CK
Lee
S Y
SY
Zhang
T F
TF
Schofield
B H
BH
Kattan
M
M
Sampson
H A
HA
Li
X M
XM
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D018122:B7-1 Antigen / Q000096:biosynthesis* / Q000235:genetics; D051940:B7-2 Antigen; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D002478:Cells, Cultured; D003207:Conalbumin / Q000008:administration & dosage / Q000276:immunology; D018899:CpG Islands / Q000276:immunology*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000276:immunology; D006965:Hyperplasia; D007136:Immunoglobulins / Q000096:biosynthesis; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D018793:Interleukin-13 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008806:Mice, Inbred AKR; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D020545:Respiratory Mucosa / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C408982:CPG-oligonucleotide; C497965:Cd86 protein, mouse; D007136:Immunoglobulins; D018793:Interleukin-13; D015848:Interleukin-5; D008562:Membrane Glycoproteins; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D003207:Conalbumin; D015847:Interleukin-4; D007371:Interferon-gamma