CpG oligodeoxynucleotides can reverse Th2-associated allergic airway responses and alter the B7.1/B7.2 expression in a murine model of asthma.

Abstract

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.

• Authors: D Serebrisky, A A Teper, C K Huang, S Y Lee, T F Zhang, B H Schofield, M Kattan, H A Sampson, X M Li
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 165 Issue 10 Pg. 5906-12 (Nov 15 2000) ISSN: 0022-1767 [Print] United States
• PMID: 11067952 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Adjuvants, Immunologic
• Antigens, CD
• B7-1 Antigen
• B7-2 Antigen
• CPG-oligonucleotide
• Cd86 protein, mouse
• Immunoglobulins
• Interleukin-13
• Interleukin-5
• Membrane Glycoproteins
• Oligodeoxyribonucleotides
• RNA, Messenger
• Conalbumin
• Interleukin-4
• Interferon-gamma

Topics

• Adjuvants, Immunologic (administration & dosage, pharmacology)
• Animals
• Antigens, CD (biosynthesis, genetics)
• Asthma (immunology, pathology)
• B7-1 Antigen (biosynthesis, genetics)
• B7-2 Antigen
• Bronchial Hyperreactivity (immunology)
• Cells, Cultured
• Conalbumin (administration & dosage, immunology)
• CpG Islands (immunology)
• Disease Models, Animal
• Down-Regulation (immunology)
• Hyperplasia
• Immunoglobulins (biosynthesis)
• Injections, Intraperitoneal
• Interferon-gamma (antagonists & inhibitors, biosynthesis)
• Interleukin-13 (biosynthesis)
• Interleukin-4 (biosynthesis)
• Interleukin-5 (biosynthesis)
• Male
• Membrane Glycoproteins (biosynthesis, genetics)
• Mice
• Mice, Inbred AKR
• Oligodeoxyribonucleotides (administration & dosage, pharmacology)
• RNA, Messenger (biosynthesis)
• Respiratory Mucosa (immunology, pathology)
• Th2 Cells (immunology)
• Up-Regulation (immunology)