Abstract
Resistin-like molecule alpha (Retnla), also known as ‘Found in inflammatory zone 1’, is a secreted protein that has been found in bronchoalveolar lavage (BAL) fluid of ovalbumin (OVA)-induced asthmatic mice and plays a role as a regulator of T helper (Th)2-driven inflammation. However, the role of Retnla in the progress of Th2-driven airway inflammation is not yet clear. To better understand the function of Retnla in Th2-driven airway inflammation, we generated Retnla-overexpressing (Retnla-Tg) mice. Retnla-Tg mice showed increased expression of Retnla protein in BAL fluid and airway epithelial cells. Retnla overexpression itself did not induce any alteration in lung histology or lung function compared to non-Tg controls. However, OVA-sensitized/challenged Retnla-Tg mice had decreased numbers of cells in BAL and inflammatory cells accumulating in the lung. They also showed a reduction in mucus production in the airway epithelium, concomitant with a decreased Muc5ac level. These results were accompanied by reduced levels of Th2 cytokines, including interleukin (IL)-4, IL-5, and IL-13, with no effect on levels of OVA-specific immunoglobulin isotypes. Furthermore, phosphorylation of ERK was markedly reduced in the lungs of OVA-challenged Retnla-Tg mice. Taken together, these results indicates that Retnla protects against Th2-mediated inflammation in an experimental mouse model of asthma, suggesting that therapeutic approaches to enhance the production of Retnla or Retnla-like molecules could be valuable for preventing allergic lung inflammation.
Highlights
Allergic asthma is a chronic inflammatory disorder of the airway, driven by an imbalance in T helper (Th) cell responses, leading to chronic airwayPLOS ONE | DOI:10.1371/journal.pone.0112666 November 21, 2014The Role of Resistin-like molecule alpha (Retnla) on Allergic Lung Inflammation inflammation, fibrosis in the lamina reticularis and adventitia of the airway, and mucus hypersecretion in the lung [1]
We attempted to determine the exact function of Retnla in asthmatic lung inflammation by generating Retnla-overexpressing transgenic mice
Since Retnla can be released into the surrounding environment to affect distant organs, we designed the Retnla-Tg vector to be controlled by the chicken b-actin promoter instead of using a tissue-specific promoter
Summary
Allergic asthma is a chronic inflammatory disorder of the airway, driven by an imbalance in T helper (Th) cell responses, leading to chronic airwayPLOS ONE | DOI:10.1371/journal.pone.0112666 November 21, 2014The Role of Retnla on Allergic Lung Inflammation inflammation, fibrosis in the lamina reticularis and adventitia of the airway, and mucus hypersecretion in the lung [1]. Resistin-like molecule alpha (Retnla), known as ‘Found in inflammatory zone 1’ or ‘Hypoxia-induced mitogenic factor’, belongs to a family of small cysteine-rich secreted proteins, including Retnla/Relm-a/FIZZ1, Retnlb/Relm-b/ FIZZ2, Resistin/FIZZ3 and Retnlg/Relm-c/FIZZ4 [3, 4]. It was initially found in bronchoalveolar lavage (BAL) fluid from mice experiencing ovalbumin (OVA)induced allergic airway inflammation. Recent work using Retnla-deficient mice showed that Retnla is dispensable for Th2-associated allergen-driven lung inflammation [16], and another study reported that recombinant Retnla increased proliferation and growth factor expression in pulmonary endothelial cells [17, 18]. Several previous papers have reported on the involvement of Retnla in airway Th2-mediated inflammatory processes, the results are heterogeneous, and the exact function of Retnla in allergic lung inflammation is not completely understood
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