Surfactant Protein-A Protects against IL-13–Induced Inflammation in Asthma

• Published in: The Journal of immunology (1950) Vol. 204; no. 10; pp. 2829 - 2839
• Main Authors: Francisco, Dave, Wang, Ying, Conway, Michelle, Hurbon, Audriana N, Dy, Alane B C, Addison, Kenneth J, Chu, Hong W, Voelker, Dennis R, Ledford, Julie G, Kraft, Monica
• Format: Journal Article
• Language: English
• Published: United States 15.05.2020
• Subjects: Animals; Asthma; Cell Movement; Cells, Cultured; Disease Models, Animal; Eosinophils - immunology; Humans; Inflammation - metabolism; Interleukin-13 - metabolism; Interleukin-6 - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Neutrophils - immunology; Pulmonary Surfactant-Associated Protein A - genetics; Pulmonary Surfactant-Associated Protein A - metabolism; Respiratory Mucosa - metabolism; Respiratory Mucosa - pathology; Signal Transduction; STAT3 Transcription Factor - metabolism
• ISSN: 0022-1767; 1550-6606; 1550-6606
• DOI: 10.4049/jimmunol.1901227

The lung surfactant proteins are recognized as critical not only for their role in lowering lung surface tension but also in innate host defense. Reports have shown that some asthmatic patients have decreased levels of one member of this protein family in particular, surfactant protein-A (SP-A). Our studies set out to determine the contribution of SP-A to the response of a key effector cytokine in asthma, IL-13. Our studies employ both animal models sufficient and deficient in SP-A challenged with IL-13 and primary epithelial cells from participants with asthma that are exogenously treated with SP-A in the context of IL-13 challenge. The inflammatory response and mucin production were assessed in both model systems. As compared with WT mice, we show that the activity of IL-13 is dramatically augmented in SP-A−/− mice, which have significantly increased neutrophil and eosinophil recruitment, mucin production and asthma-associated cytokines in the bronchoalveolar lavage fluid. In parallel, we show asthma-associated factors are attenuated in human cells from asthma subjects when exogenous SP-A is added during IL-13 challenge. Although many of these phenotypes have previously been associated with STAT6 signaling, SP-A inhibited IL-13-induced STAT3 phosphorylation in mice and in human epithelial cells while having little effect on STAT6 phosphorylation. In addition, when either STAT3 or IL-6 were inhibited in mice, the phenotypes observed in SP-A−/− mice were significantly attenuated. These studies suggest a novel mechanism for SP-A in asthma as a modulator of IL-13-induced inflammation via mediating downstream IL-6/STAT3 signaling.