Apolipoprotein A-IV is a candidate target molecule for the treatment of seasonal allergic rhinitis

Makino, Yuka; Noguchi, Emiko; Takahashi, Noboru; Matsumoto, Yuri; Kubo, Shigeru; Yamada, Tetsuji; Imoto, Yoshimasa; Ito, Yatsuji; Osawa, Yusuke; Shibasaki, Masanao; Uchida, Keiji; Meno, Kohji; Suzuki, Hideaki; Okubo, Kimihiro; Arinami, Tadao; Fujieda, Shigeharu

doi:10.1016/j.jaci.2010.06.031

Cited by 30 publications

(37 citation statements)

References 31 publications

(30 reference statements)

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“…Upregulation of apolipoprotein A-IV (ApoA-IV) in serum in pollinosis patients from pre- to postpollen season was found to be significantly greater with SLIT than with placebo and was inversely correlated with SMS and QOL scores in the SLIT group [70]. ApoA-IV also significantly reduces histamine release in vitro from basophils taken from patients [70], and ApoA-IV induced by SLIT may be involved in downregulation of local or peripheral inflammation during the pollen season.…”

Section: Recent Findings On Biomarkers For Slitmentioning

confidence: 99%

Therapeutic Effects and Biomarkers in Sublingual Immunotherapy: A Review

2012

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Immunotherapy is considered to be the only curative treatment for allergic diseases such as pollinosis, perennial rhinitis, asthma, and food allergy. The sublingual route is widely applied for immunotherapy for allergy, instead of the conventional administration by subcutaneous route. A recent meta-analysis of sublingual immunotherapy (SLIT) has shown that this approach is safe, has positive clinical effects, and provides prolonged therapeutic effects after discontinuation of treatment. However, the mechanism of SLIT and associated biomarkers are not fully understood. Biomarkers that change after or during SLIT have been reported and may be useful for response monitoring or as prognostic indicators for SLIT. In this review, we focus on the safety, therapeutic effects, including prolonged effects after treatment, and new methods of SLIT. We also discuss response monitoring and prognostic biomarkers for SLIT. Finally, we discuss immunological mechanisms of SLIT with a focus on oral dendritic cells and facilitated antigen presentation.

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Section: Recent Findings On Biomarkers For Slitmentioning

confidence: 99%

Therapeutic Effects and Biomarkers in Sublingual Immunotherapy: A Review

2012

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“…ApoA‐IV levels have been shown to increase under immunotherapy in patients with allergic rhinitis . However, ApoA‐IV serum levels in allergic patients and healthy controls have not been compared yet.…”

Section: Resultsmentioning

confidence: 99%

Apolipoprotein A‐IV acts as an endogenous anti‐inflammatory protein and is reduced in treatment‐naïve allergic patients and allergen‐challenged mice

Roula

Theiler

Luschnig

et al. 2019

Allergy

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Background Recent studies pointed to a crucial role for apolipoproteins in the pathogenesis of inflammatory diseases. However, the role of apolipoprotein‐IV (ApoA‐IV) in allergic inflammation has not been addressed thoroughly thus far. Objective Here, we explored the anti‐inflammatory effects and underlying signaling pathways of ApoA‐IV on eosinophil effector function in vitro and in vivo. Methods Migratory responsiveness, Ca2+‐flux and apoptosis of human peripheral blood eosinophils were assessed in vitro. Allergen‐driven airway inflammation was assessed in a mouse model of acute house dust mite‐induced asthma. ApoA‐IV serum levels were determined by ELISA. Results Recombinant ApoA‐IV potently inhibited eosinophil responsiveness in vitro as measured by Ca2+‐flux, shape change, integrin (CD11b) expression, and chemotaxis. The underlying molecular mechanism involved the activation of Rev‐ErbA‐α and induced a PI3K/PDK1/PKA‐dependent signaling cascade. Systemic application of ApoA‐IV prevented airway hyperresponsiveness (AHR) and airway eosinophilia in mice following allergen challenge. ApoA‐IV levels were decreased in serum from allergic patients compared to healthy controls. Conclusion Our data suggest that ApoA‐IV is an endogenous anti‐inflammatory protein that potently suppresses effector cell functions in eosinophils. Thus, exogenously applied ApoA‐IV may represent a novel pharmacological approach for the treatment of allergic inflammation and other eosinophil‐driven disorders.

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“…80,81 SIT reduces mast cell, basophil and neutrophil activation and IgE-mediated release of preformed and newly generated mediators by mast cells and basophils. [80][81][82][83] Moreover, SIT inhibits the number and function of eosinophils, 84 mitigates eosinophil and neutrophil migration to the site of allergic reaction, 84 and reduces priming of eosinophil adhesion during allergen season. 85 IL-10 seems to plays a key in the anti-inflammatory actions on tissue cells, as it was shown to reduce degranulation of mast cells 83 and a reduction of eosinophil chemotactic IL-5 production by Th2 cells.…”

Section: Regulation Of Allergen-specific Ige and Igg4mentioning

confidence: 99%