SPLUNC1 deficiency enhances airway eosinophilic inflammation in mice.

Abstract

Short palate, lung and nasal epithelium clone 1 (SPLUNC1) is enriched in normal airway lining fluid, but is significantly reduced in airway epithelium exposed to a Th2 cytokine milieu. The role of SPLUNC1 in modulating airway allergic inflammation (e.g., eosinophils) remains unknown. We used SPLUNC1 knockout (KO) and littermate wild-type (C57BL/6 background) mice and recombinant SPLUNC1 protein to determine the impact of SPLUNC1 on airway allergic/eosinophilic inflammation, and to investigate the underlying mechanisms. An acute ovalbumin (OVA) sensitization and challenge protocol was used to induce murine airway allergic inflammation (e.g., eosinophils, eotaxin-2, and Th2 cytokines). Our results showed that SPLUNC1 in the bronchoalveolar lavage fluid of OVA-challenged wild-type mice was significantly reduced (P < 0.05), which was negatively correlated with levels of lung eosinophilic inflammation. Moreover, SPLUNC1 KO mice demonstrated significantly higher numbers of eosinophils in the lung after OVA challenges than did wild-type mice. Alveolar macrophages isolated from OVA-challenged SPLUNC1 KO versus wild-type mice had higher concentrations of baseline eotaxin-2 that was amplified by LPS (a known risk factor for exacerbating asthma). Human recombinant SPLUNC1 protein was applied to alveolar macrophages to study the regulation of eotaxin-2 in the context of Th2 cytokine and LPS stimulation. Recombinant SPLUNC1 protein attenuated LPS-induced eotaxin-2 production in Th2 cytokine-pretreated murine macrophages. These findings demonstrate that SPLUNC1 inhibits airway eosinophilic inflammation in allergic mice, in part by reducing eotaxin-2 production in alveolar macrophages.

• Authors: Jyoti V Thaikoottathil, Richard J Martin, Peter Y Di, Maisha Minor, Stephanie Case, Bicheng Zhang, Gongyi Zhang, Hua Huang, Hong Wei Chu
• Journal: American journal of respiratory cell and molecular biology (Am J Respir Cell Mol Biol) Vol. 47 Issue 2 Pg. 253-60 (Aug 2012) ISSN: 1535-4989 [Electronic] United States
• PMID: 22499853 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Bpifa1 protein, mouse
• Chemokine CCL24
• Glycoproteins
• Interleukin-13
• Lipopolysaccharides
• Phosphoproteins
• Recombinant Proteins
• Interleukin-4
• Ovalbumin

Topics

• Animals
• Bronchoalveolar Lavage Fluid (immunology)
• Chemokine CCL24 (immunology, metabolism)
• Eosinophils (immunology, metabolism)
• Glycoproteins (deficiency, immunology, metabolism)
• HEK293 Cells
• Humans
• Interleukin-13 (immunology, metabolism)
• Interleukin-4 (immunology, metabolism)
• Lipopolysaccharides (immunology)
• Lung (immunology, metabolism)
• Macrophages, Alveolar (immunology, metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Ovalbumin (immunology)
• Phosphoproteins (deficiency, immunology, metabolism)
• Pneumonia (immunology, metabolism)
• Recombinant Proteins (immunology, metabolism)
• Th2 Cells (immunology, metabolism)