Surfactant protein D prevents mucin overproduction in airway goblet cells via SIRPα
Abstract Mucin overproduction is a common feature of chronic airway diseases such as asthma and chronic obstructive pulmonary disease (COPD), and exacerbates their underlying respiratory condition. Surfactant protein D (SP-D) protects against airway diseases through modulation of immune reactions, b...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-52328-5 |
| _version_ | 1797350011679277056 |
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| author | Kentaro Hata Kazuya Tsubouchi Kunihiro Suzuki Daisuke Eto Hiroyuki Ando Toyoshi Yanagihara Keiko Kan-o Isamu Okamoto |
| author_facet | Kentaro Hata Kazuya Tsubouchi Kunihiro Suzuki Daisuke Eto Hiroyuki Ando Toyoshi Yanagihara Keiko Kan-o Isamu Okamoto |
| author_sort | Kentaro Hata |
| collection | DOAJ |
| description | Abstract Mucin overproduction is a common feature of chronic airway diseases such as asthma and chronic obstructive pulmonary disease (COPD), and exacerbates their underlying respiratory condition. Surfactant protein D (SP-D) protects against airway diseases through modulation of immune reactions, but whether it also exerts direct effects on airway epithelial cells has remained unclear. Therefore, we sought to investigate the inhibitory role of SP-D on mucin production in airway epithelial cells. We prepared air–liquid interface (ALI) cultures of human primary bronchial epithelial cells (HBECs), which recapitulated a well-differentiated human airway epithelium. Benzo(a)pyrene (BaP), a key toxicant in cigarette smoke, induced mucin 5AC (MUC5AC) production in ALI-cultured HBECs, airway secretory cell lines, and airway epithelia of mice. Then, the protective effects of SP-D against the BaP-induced mucin overproduction were examined. BaP increased MUC5AC production in ALI cultures of HBECs, and this effect was attenuated by SP-D. SP-D also suppressed the BaP-induced phosphorylation of extracellular signal-regulated kinase (ERK) and MUC5AC expression in NCI-H292 goblet-like cells, but not in NCI-H441 club-like cells. Signal regulatory protein α (SIRPα) was found to be expressed in HBECs and NCI-H292 cells but absent in NCI-H441 cells. In NCI-H292 cells, SP-D activated SH2 domain-containing tyrosine phosphatase-1 (SHP-1), downstream of SIRPα, and knockdown of SIRPα abolished the suppressive effects of SP-D on BaP-induced ERK phosphorylation and MUC5AC production. Consistent with these in vitro findings, intratracheal instillation of SP-D prevented the BaP-induced phosphorylation of ERK and Muc5ac expression in airway epithelial cells in a mouse model. SP-D acts directly on airway epithelial cells to inhibit mucin secretion through ligation of SIRPα and SHP-1-mediated dephosphorylation of ERK. Targeting of SIRPα is therefore a potential new therapeutic approach to suppression of mucin hypersecretion in chronic airway diseases such as COPD and asthma. |
| first_indexed | 2024-03-08T12:38:37Z |
| format | Article |
| id | doaj.art-9e65eed894cd4367acf8b18b284235c6 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-08T12:38:37Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-9e65eed894cd4367acf8b18b284235c62024-01-21T12:18:28ZengNature PortfolioScientific Reports2045-23222024-01-0114111210.1038/s41598-024-52328-5Surfactant protein D prevents mucin overproduction in airway goblet cells via SIRPαKentaro Hata0Kazuya Tsubouchi1Kunihiro Suzuki2Daisuke Eto3Hiroyuki Ando4Toyoshi Yanagihara5Keiko Kan-o6Isamu Okamoto7Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu UniversityDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu UniversityDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu UniversityDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu UniversityDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu UniversityDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu UniversityDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu UniversityDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu UniversityAbstract Mucin overproduction is a common feature of chronic airway diseases such as asthma and chronic obstructive pulmonary disease (COPD), and exacerbates their underlying respiratory condition. Surfactant protein D (SP-D) protects against airway diseases through modulation of immune reactions, but whether it also exerts direct effects on airway epithelial cells has remained unclear. Therefore, we sought to investigate the inhibitory role of SP-D on mucin production in airway epithelial cells. We prepared air–liquid interface (ALI) cultures of human primary bronchial epithelial cells (HBECs), which recapitulated a well-differentiated human airway epithelium. Benzo(a)pyrene (BaP), a key toxicant in cigarette smoke, induced mucin 5AC (MUC5AC) production in ALI-cultured HBECs, airway secretory cell lines, and airway epithelia of mice. Then, the protective effects of SP-D against the BaP-induced mucin overproduction were examined. BaP increased MUC5AC production in ALI cultures of HBECs, and this effect was attenuated by SP-D. SP-D also suppressed the BaP-induced phosphorylation of extracellular signal-regulated kinase (ERK) and MUC5AC expression in NCI-H292 goblet-like cells, but not in NCI-H441 club-like cells. Signal regulatory protein α (SIRPα) was found to be expressed in HBECs and NCI-H292 cells but absent in NCI-H441 cells. In NCI-H292 cells, SP-D activated SH2 domain-containing tyrosine phosphatase-1 (SHP-1), downstream of SIRPα, and knockdown of SIRPα abolished the suppressive effects of SP-D on BaP-induced ERK phosphorylation and MUC5AC production. Consistent with these in vitro findings, intratracheal instillation of SP-D prevented the BaP-induced phosphorylation of ERK and Muc5ac expression in airway epithelial cells in a mouse model. SP-D acts directly on airway epithelial cells to inhibit mucin secretion through ligation of SIRPα and SHP-1-mediated dephosphorylation of ERK. Targeting of SIRPα is therefore a potential new therapeutic approach to suppression of mucin hypersecretion in chronic airway diseases such as COPD and asthma.https://doi.org/10.1038/s41598-024-52328-5 |
| spellingShingle | Kentaro Hata Kazuya Tsubouchi Kunihiro Suzuki Daisuke Eto Hiroyuki Ando Toyoshi Yanagihara Keiko Kan-o Isamu Okamoto Surfactant protein D prevents mucin overproduction in airway goblet cells via SIRPα Scientific Reports |
| title | Surfactant protein D prevents mucin overproduction in airway goblet cells via SIRPα |
| title_full | Surfactant protein D prevents mucin overproduction in airway goblet cells via SIRPα |
| title_fullStr | Surfactant protein D prevents mucin overproduction in airway goblet cells via SIRPα |
| title_full_unstemmed | Surfactant protein D prevents mucin overproduction in airway goblet cells via SIRPα |
| title_short | Surfactant protein D prevents mucin overproduction in airway goblet cells via SIRPα |
| title_sort | surfactant protein d prevents mucin overproduction in airway goblet cells via sirpα |
| url | https://doi.org/10.1038/s41598-024-52328-5 |
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