CpG oligodeoxynucleotides do not require TH1 cytokines to prevent eosinophilic airway inflammation in a murine model of asthma☆,☆☆,★
Section snippets
Animals and murine model of asthma
Six-week-old female C57BL/6 mice were obtained from Jackson Laboratories (Bar Harbor, Me). All animal care and housing requirements of the National Institutes of Health Committee on Care and Use of Laboratory Animals were followed. For some studies, mice on a C57BL/6 genetic background with disrupted genes for IFN-γ (C57BL/6-Ifng tm1Ts, Jackson Laboratory)10 or IL-12 (C57BL/6-Il12 atm1Jm, Jackson Laboratory)11 were used. The IFN-γ knockout mice produce no IFN-γ; the IL-12 knockout mice produce
ELISA
Murine IL-4 and IL-5 were measured by using a sandwich ELISA (R&D) according to the manufacturer’s instructions.
Effect of TH1 cytokines on airway eosinophilia and bronchial hyperreactivity
To ascertain whether TH1 cytokines were capable of preventing the development of TH2-mediated airway eosinophilia in the schistosome egg-SEA murine asthma model, we first examined the effects of administering IFN-γ and IL-12 at various time points relative to sensitization and airway challenge with schistosome eggs and SEA. We found that treatment with IL-12 (1 μg administered intraperitoneally on days 0, 1, 2, and 3), as well as with IFN-γ (10,000 U administered intraperitoneally on days 0, 1,
DISCUSSION
Immunostimulatory CpG-ODNs have a wide range of effects on inflammation and immune responses.8, 16, 17, 18, 19, 20 Recently, we have shown that CpG-ODNs are also effective in prevention of eosinophilic airway inflammation in a murine model of asthma.9 Most of these actions of CpG-ODNs have been associated with, or attributed to, the induction of a TH1-like immune response. This response is characterized by production of IFN-γ and IL-12. To evaluate whether the association between the TH1
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Nucleic Acid Sensing in Allergic Disorders
2019, International Review of Cell and Molecular BiologyCitation Excerpt :The immune therapeutic role of CpG ODNs is believed to be partly attributed to their potential in initiating a TH1 biased adaptive immune response and releasing cytokines such as IL-12 and IFN-γ; hence, reversing and preventing the hallmark TH2 immune response of allergic diseases. In murine models of acute atopic asthma CpG ODN administration with antigen inhibits the synthesis of IL-4 and IL-5, as well as eosinophilia and AHR (Hussain et al., 2002; Kline et al., 1998, 1999; Sur et al., 1999). In an allergic mouse model of asthma induced by ragweed, administration of CpG 48 h before allergen challenge conferred protection from the TH2 allergic response by inducing a TH1 response thereby reducing the number of the cells producing ragweed allergen-specific IgE (Sur et al., 1999).
The interstitial macrophage: A long-neglected piece in the puzzle of lung immunity
2018, Cellular ImmunologyCritical role of Toll-like receptors in pathophysiology of allergic asthma
2017, European Journal of PharmacologyPerspectives in vaccine adjuvants for allergen-specific immunotherapy
2014, Immunology LettersTLR agonist mediated suppression of allergic responses is associated with increased innate inflammation in the airways
2011, Pulmonary Pharmacology and TherapeuticsCitation Excerpt :TLR1, TLR2, TLR4, TLR5, TLR6, TLR10 and TLR11 are expressed on the cell surface, whereas TLR3, TLR7, TLR8 and TLR9 are expressed within the cells [6]. Animal studies have shown that the application of certain TLR agonists can suppress the development of asthma and allergic responses [7–25]. The most widely studied TLR agonists are agonists of TLR2, TLR3, TLR4, TLR7, and TLR9.
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Supported by grants from the National Institutes of Health (HL59324, HL02950, and ES05605), the American Lung Association, the Department of Veteran’s Affairs (Career Award), the Center for Advanced Studies-Spellman Rockefeller, and CpG Immunopharmaceuticals.
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Reprint requests: Joel N. Kline, MD, C33GH UIHC, Iowa City, IA 52242.
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