Secreted hCLCA1 is a signaling molecule that activates airway macrophages.
The CLCA gene family produces both secreted and membrane-associated proteins that modulate ion-channel function, drive mucus production and have a poorly understood pleiotropic effect on airway inflammation. The primary up-regulated human CLCA ortholog in airway inflammation is hCLCA1. Here we show...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3861482?pdf=render |
| _version_ | 1818049332716240896 |
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| author | John C H Ching Liubov Lobanova Matthew E Loewen |
| author_facet | John C H Ching Liubov Lobanova Matthew E Loewen |
| author_sort | John C H Ching |
| collection | DOAJ |
| description | The CLCA gene family produces both secreted and membrane-associated proteins that modulate ion-channel function, drive mucus production and have a poorly understood pleiotropic effect on airway inflammation. The primary up-regulated human CLCA ortholog in airway inflammation is hCLCA1. Here we show that this protein can activate airway macrophages, inducing them to express cytokines and to undertake a pivotal role in airway inflammation. In a U-937 airway macrophage-monocyte cell line, conditioned media from HEK 293 cells heterologously expressing hCLCA1 (with or without fetal bovine serum) increased the levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α and IL-8). This effect was independent of the metalloprotease domain of hCLCA1. Primary porcine alveolar macrophages were similarly activated, demonstrating the effect was not cell line dependent. Similarly, immuno-purified hCLCA1 at physiologically relevant concentration of ~100 pg/mL was able to activate macrophages and induce pro-inflammatory response. This cytokine response increased with higher concentration of immuno-purified hCLCA1. These findings demonstrate the ability of hCLCA1 to function as a signaling molecule and activate macrophages, central regulators of airway inflammation. |
| first_indexed | 2024-12-10T10:35:54Z |
| format | Article |
| id | doaj.art-4e9b72d9ef49463d9ca496e38c4bbfbd |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T10:35:54Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-4e9b72d9ef49463d9ca496e38c4bbfbd2022-12-22T01:52:25ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01812e8313010.1371/journal.pone.0083130Secreted hCLCA1 is a signaling molecule that activates airway macrophages.John C H ChingLiubov LobanovaMatthew E LoewenThe CLCA gene family produces both secreted and membrane-associated proteins that modulate ion-channel function, drive mucus production and have a poorly understood pleiotropic effect on airway inflammation. The primary up-regulated human CLCA ortholog in airway inflammation is hCLCA1. Here we show that this protein can activate airway macrophages, inducing them to express cytokines and to undertake a pivotal role in airway inflammation. In a U-937 airway macrophage-monocyte cell line, conditioned media from HEK 293 cells heterologously expressing hCLCA1 (with or without fetal bovine serum) increased the levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α and IL-8). This effect was independent of the metalloprotease domain of hCLCA1. Primary porcine alveolar macrophages were similarly activated, demonstrating the effect was not cell line dependent. Similarly, immuno-purified hCLCA1 at physiologically relevant concentration of ~100 pg/mL was able to activate macrophages and induce pro-inflammatory response. This cytokine response increased with higher concentration of immuno-purified hCLCA1. These findings demonstrate the ability of hCLCA1 to function as a signaling molecule and activate macrophages, central regulators of airway inflammation.http://europepmc.org/articles/PMC3861482?pdf=render |
| spellingShingle | John C H Ching Liubov Lobanova Matthew E Loewen Secreted hCLCA1 is a signaling molecule that activates airway macrophages. PLoS ONE |
| title | Secreted hCLCA1 is a signaling molecule that activates airway macrophages. |
| title_full | Secreted hCLCA1 is a signaling molecule that activates airway macrophages. |
| title_fullStr | Secreted hCLCA1 is a signaling molecule that activates airway macrophages. |
| title_full_unstemmed | Secreted hCLCA1 is a signaling molecule that activates airway macrophages. |
| title_short | Secreted hCLCA1 is a signaling molecule that activates airway macrophages. |
| title_sort | secreted hclca1 is a signaling molecule that activates airway macrophages |
| url | http://europepmc.org/articles/PMC3861482?pdf=render |
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