The role of prostaglandins in allergic lung inflammation and asthma

We identify the tumor necrosis factor receptor superfamily 25 (TNFRSF25)/TNFSF15 pair as critical trigger for allergic lung inflammation, which is a cardinal feature of asthma. TNFRSF25 (TNFR25) signals are required to exert T helper cell 2 (Th2) effector function in Th2-polarized CD4 cells and co-stimulate interleukin (IL)-13 production by glycosphingolipid-activated NKT cells. In vivo, antibody blockade of TNFSF15 (TL1A), which is the ligand for TNFR25, inhibits lung inflammation and production of Th2 cytokines such as IL-13, even when administered days after airway antigen exposure. Similarly, blockade of TNFR25 by a dominant-negative (DN) transgene, DN TNFR25, confers resistance to lung inflammation in mice. Allergic lung inflammation–resistant, NKT-deficient mice become susceptible upon adoptive transfer of wild-type NKT cells, but not after transfer of DN TNFR25 transgenic NKT cells. The TNFR25/TL1A pair appears to provide an early signal for Th2 cytokine production in the lung, and therefore may be a drug target in attempts to attenuate lung inflammation in asthmatics.

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Faculty Opinions recommendation of Dual role of YM1+ M2 macrophages in allergic lung inflammation.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.732895700.793562395 ◽

2019 ◽

Author(s):

Nicola Heller ◽

Hosam Arammash

Keyword(s):

Lung Inflammation ◽

Dual Role ◽

M2 Macrophages ◽

Allergic Lung Inflammation

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Cellular recruitment and cytokine generation in a rat model of allergic lung inflammation are differentially modulated by progesterone and estradiol

AJP Cell Physiology ◽

10.1152/ajpcell.00286.2006 ◽

2007 ◽

Vol 293 (3) ◽

pp. C1120-C1128 ◽

Cited By ~ 45

Author(s):

Ana Paula Ligeiro de Oliveira ◽

Helori Vanni Domingos ◽

Gabriela Cavriani ◽

Amilcar Sabino Damazo ◽

Adriana Lino dos Santos Franco ◽

...

Keyword(s):

Lung Inflammation ◽

Estradiol Treatment ◽

Cell Recruitment ◽

Ovx Rats ◽

Allergic Lung Inflammation ◽

Tnf Α ◽

Cellular Recruitment ◽

Additional Reduction

We evaluated the role of estradiol and progesterone in allergic lung inflammation. Rats were ovariectomized (Ovx) and, 7 days later, were sensitized with ovalbumin (OA) and challenged after 2 wk with inhaled OA; experiments were performed 1 day thereafter. Ovx-allergic rats showed reduced cell recruitment into the bronchoalveolar lavage (BAL) fluid relative to sham-Ovx allergic rats, as was observed in intact allergic rats treated with ICI-182,780. Estradiol increased the number of cells in the BAL of Ovx-allergic rats, whereas progesterone induced an additional reduction. Cells of BAL and bone marrow (BM) of Ovx-allergic rats released elevated amounts of IL-10 and reduced IL-1β and TNF-α. BM cells of Ovx-allergic rats released increased amounts of IL-10 and lower amounts of IL-4. Estradiol treatment of Ovx-allergic rats decreased the release of IL-10 but increased that of IL-4 by BM cells. Estradiol also caused an increased release of IL-1β and TNF-α by BAL cells. Progesterone significantly increased the release of IL-10, IL-1β, and TNF-α by BAL cells and augmented that of IL-4 by BM cells. Degranulation of bronchial mast cells from Ovx rats was reduced after in vitro challenge, an effect reverted by estradiol but not by progesterone. We suggest that the serum estradiol-to-progesterone ratio might drive cellular recruitment, modulating the pulmonary allergy and profile of release of anti-inflammatory or inflammatory cytokines. The existence of such dual hormonal effects suggests that the hormone therapy of asthmatic postmenopausal women and of those suffering of premenstrual asthma should take into account the possibility of worsening the pulmonary conditions.

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Dual role of YM1+ M2 macrophages in allergic lung inflammation

Scientific Reports ◽

10.1038/s41598-018-23269-7 ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 13

Author(s):

Christina Draijer ◽

Patricia Robbe ◽

Carian E. Boorsma ◽

Machteld N. Hylkema ◽

Barbro N. Melgert

Keyword(s):

Lung Inflammation ◽

Dual Role ◽

M2 Macrophages ◽

Allergic Lung Inflammation

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Update on the role of prostaglandins in allergic lung inflammation: Separating friends from foes, harder than you might think

Journal of Allergy and Clinical Immunology ◽

10.1016/j.jaci.2005.12.1314 ◽

2006 ◽

Vol 117 (5) ◽

pp. 1036-1039 ◽

Cited By ~ 33

Author(s):

Martin L. Moore ◽

R. Stokes Peebles

Keyword(s):

Lung Inflammation ◽

Allergic Lung Inflammation

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The Role of α 4 (CD49d) and β 2 (CD18) Integrins in Eosinophil and Neutrophil Migration to Allergic Lung Inflammation in the Brown Norway Rat

American Journal of Respiratory Cell and Molecular Biology ◽

10.1165/ajrcmb.20.3.3207 ◽

1999 ◽

Vol 20 (3) ◽

pp. 448-457 ◽

Cited By ~ 30

Author(s):

Thorsten Schneider ◽

Thomas B. Issekutz ◽

Andrew C. Issekutz

Keyword(s):

Lung Inflammation ◽

Neutrophil Migration ◽

Brown Norway ◽

Norway Rat ◽

Allergic Lung Inflammation ◽

Brown Norway Rat

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Reduced allergic lung inflammation and airway responsiveness in mice lacking the cytoskeletal protein gelsolin

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00065.2020 ◽

2020 ◽

Vol 319 (5) ◽

pp. L833-L842

Author(s):

Maya Mikami ◽

Gene T. Yocum ◽

Nicola M. Heller ◽

Charles W. Emala

Keyword(s):

Airway Inflammation ◽

Lung Inflammation ◽

Ex Vivo ◽

Cell Types ◽

Asthma Severity ◽

Wild Type ◽

Allergic Lung Inflammation ◽

Actin Capping

Airway smooth muscle hyperresponsiveness associated with chronic airway inflammation leads to the typical symptoms of asthma including bronchoconstriction and wheezing. Asthma severity is associated with airway inflammation; therefore, reducing airway inflammation is an important therapeutic target. Gelsolin is an actin capping and severing protein that has been reported to be involved in modulation of the inflammatory response. Using mice genetically lacking gelsolin, we evaluated the role of gelsolin in the establishment of house dust mite (HDM) antigen-induced allergic lung inflammation. The genetic absence of gelsolin was found to be protective against HDM sensitization, resulting in reduced lung inflammation, inflammatory cytokines, and Muc5AC protein in bronchoalveolar lavage (BAL) fluid. The number of eosinophils, lymphocytes, and interstitial macrophages in the BAL were increased after HDM sensitization in wild-type mice but were attenuated in gelsolin-null mice. The observed attenuation of inflammation may be partly due to delayed migration of immune cells, because the reduced eosinophils in the BALs from gelsolin-null mice compared with controls occurred despite similar amounts of the chemoattractant eotaxin. Splenic T cells demonstrated similar proliferation rates, but ex vivo alveolar macrophage migration was delayed in gelsolin-null mice. In vivo, the reduced lung inflammation after HDM sensitization in gelsolin-null mice was associated with significantly diminished airway resistance to inhaled methacholine compared with HDM-treated wild-type mice. Our results suggest that modulation of gelsolin expression or function in selective inflammatory cell types that modulate allergic lung inflammation could be a therapeutic approach for asthma.

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Role of Galectin-3 in the pathophysiology underlying allergic lung inflammation in a tissue inhibitor of metalloproteinases 1 knockout model of murine asthma

Immunology ◽

10.1111/imm.12848 ◽

2017 ◽

Vol 153 (3) ◽

pp. 387-396 ◽

Cited By ~ 2

Author(s):

Manoj J. Mammen ◽

Mark F. Sands ◽

Elaine Abou-Jaoude ◽

Ravikumar Aalinkeel ◽

Jessica L. Reynolds ◽

...

Keyword(s):

Lung Inflammation ◽

Tissue Inhibitor Of Metalloproteinases ◽

Tissue Inhibitor ◽

Allergic Lung Inflammation ◽

Galectin 3 ◽

Knockout Model

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Airway epithelial phosphoinositide 3-kinase-δ contributes to the modulation of fungi-induced innate immune response

Thorax ◽

10.1136/thoraxjnl-2017-210326 ◽

2018 ◽

Vol 73 (8) ◽

pp. 758-768 ◽

Cited By ~ 6

Author(s):

Jae Seok Jeong ◽

Kyung Bae Lee ◽

So Ri Kim ◽

Dong Im Kim ◽

Hae Jin Park ◽

...

Keyword(s):

Epithelial Cells ◽

Nlrp3 Inflammasome ◽

Airway Epithelium ◽

Lung Inflammation ◽

Allergic Inflammation ◽

Innate Immune ◽

In Vivo Models ◽

Allergic Lung Inflammation ◽

Phosphoinositide 3 Kinase

BackgroundRespiratory fungal exposure is known to be associated with severe allergic lung inflammation. Airway epithelium is an essential controller of allergic inflammation. An innate immune recognition receptor, nucleotide-binding domain, leucine-rich-containing family, pyrin-domain-containing-3 (NLRP3) inflammasome, and phosphoinositide 3 kinase (PI3K)-δ in airway epithelium are involved in various inflammatory processes.ObjectivesWe investigated the role of NLRP3 inflammasome in fungi-induced allergic lung inflammation and examined the regulatory mechanism of NLRP3 inflammasome, focusing on PI3K-δ in airway epithelium.MethodsWe used two in vivo models induced by exposure to Aspergillus fumigatus (Af) and Alternaria alternata (Aa), as well as an Af-exposed in vitro system. We also checked NLRP3 expression in lung tissues from patients with allergic bronchopulmonary aspergillosis (ABPA).ResultsAssembly/activation of NLRP3 inflammasome was increased in the lung of Af-exposed mice. Elevation of NLRP3 inflammasome assembly/activation was observed in Af-stimulated murine and human epithelial cells. Similarly, pulmonary expression of NLRP3 in patients with ABPA was increased. Importantly, neutralisation of NLRP3 inflammasome derived IL-1β alleviated pathophysiological features of Af-induced allergic inflammation. Furthermore, PI3K-δ blockade improved Af-induced allergic inflammation through modulation of NLRP3 inflammasome, especially in epithelial cells. This modulatory role of PI3K-δ was mediated through the regulation of mitochondrial reactive oxygen species (mtROS) generation. NLRP3 inflammasome was also implicated in Aa-induced eosinophilic allergic inflammation, which was improved by PI3K-δ blockade.ConclusionThese findings demonstrate that fungi-induced assembly/activation of NLRP3 inflammasome in airway epithelium may be modulated by PI3K-δ, which is mediated partly through the regulation of mtROS generation. Inhibition of PI3K-δ may have potential for treating fungi-induced severe allergic lung inflammation.

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