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PMID: 11067952 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

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

Journal of immunology (Baltimore, Md. : 1950) ·Vol. 165 ·No. 10 ·2000-11-15 ·Pages 5906-12

Serebrisky D, Teper AA, Huang CK, Lee SY, Zhang TF, Schofield BH, Kattan M, Sampson HA, Li XM

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.

MeSH Terms
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
Chemicals
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
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Serebrisky D
Department of Pediatrics, Mount Sinai School of Medicine, New York, NY 10029, USA.
Teper A A
Huang C K
Lee S Y
Zhang T F
Schofield B H
Kattan M
Sampson H A
Li X M
Article Info
Journal
Journal of immunology (Baltimore, Md. : 1950)
Abbr.
J Immunol
ISSN
0022-1767
Published
2000-11-15
Pages
5906-12
Language
English
Region
United States
NLM ID
2985117R
Subset
IM
Grants
NIAID NIH HHS · AI 43668 · United States
NIEHS NIH HHS · ES03819 · United States
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