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Inhaled iloprost suppresses the cardinal features of asthma via inhibition of airway dendritic cell function
Marco Idzko, … , Henk C. Hoogsteden, Bart N. Lambrecht
Marco Idzko, … , Henk C. Hoogsteden, Bart N. Lambrecht
Published February 1, 2007
Citation Information: J Clin Invest. 2007;117(2):464-472. https://doi.org/10.1172/JCI28949.
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Research Article Immunology Article has an altmetric score of 10

Inhaled iloprost suppresses the cardinal features of asthma via inhibition of airway dendritic cell function

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Abstract

Inhalation of iloprost, a stable prostacyclin (PGI2) analog, is a well-accepted and safe treatment for pulmonary arterial hypertension. Although iloprost mainly acts as a vasodilator by binding to the I prostanoid (IP) receptor, recent evidence suggests that signaling via this receptor also has antiinflammatory effects through unclear mechanisms. Here we show in a murine model of asthma that iloprost inhalation suppressed the cardinal features of asthma when given during the priming or challenge phase. As a mechanism of action, iloprost interfered with the function of lung myeloid DCs, critical antigen-presenting cells of the airways. Iloprost treatment inhibited the maturation and migration of lung DCs to the mediastinal LNs, thereby abolishing the induction of an allergen-specific Th2 response in these nodes. The effect of iloprost was DC autonomous, as iloprost-treated DCs no longer induced Th2 differentiation from naive T cells or boosted effector cytokine production in primed Th2 cells. These data should pave the way for a clinical effectiveness study using inhaled iloprost for the treatment of asthma.

Authors

Marco Idzko, Hamida Hammad, Menno van Nimwegen, Mirjam Kool, Nanda Vos, Henk C. Hoogsteden, Bart N. Lambrecht

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Figure 4

Administration of iloprost prevents sensitization induced by DCs.

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Administration of iloprost prevents sensitization induced by DCs.
On day...
On day 0, mice received an i.t. injection of OVA in the presence or absence of iloprost. From days –1 to 2, mice were injected i.p. with anti–Gr-1 Abs to deplete pDCs or isotype control Abs. Ten days later, mice were exposed to 3 OVA aerosols. (A) BAL fluid was analyzed by flow cytometry. (B) Hematoxylin and eosin staining of lung sections. (C) MLN cells restimulated in vitro for 4 days with OVA, and cytokines were measured in the supernatant. Data are mean ± SEM. *P < 0.05; **P < 0.01; ***P < 0.001.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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