Role of the IL-33/ST2/p38 signaling pathway in the immune response of corneal epithelial cells to Aspergillus fumigatus infection
AIM: To investigate the expression of interleukin (IL)-33 in the cornea and human corneal epithelial cells (HCECs) exposed to Aspergillus fumigatus (A. fumigatus), and to determine the function of IL-33/ST2/p38 signaling pathway in the immune response of corneal epithelial cells to A. fumigatus infe...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Press of International Journal of Ophthalmology (IJO PRESS)
2019-04-01
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| Series: | International Journal of Ophthalmology |
| Subjects: | |
| Online Access: | http://www.ijo.cn/en_publish/2019/4/20190404.pdf |
| _version_ | 1818959541104017408 |
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| author | Jia You Jing Lin Yi-Fan Zhou Xu-Dong Peng Hong He Cui Li Guo-Qiang Zhu Xue-Qi Zhao Gui-Qiu Zhao |
| author_facet | Jia You Jing Lin Yi-Fan Zhou Xu-Dong Peng Hong He Cui Li Guo-Qiang Zhu Xue-Qi Zhao Gui-Qiu Zhao |
| author_sort | Jia You |
| collection | DOAJ |
| description | AIM: To investigate the expression of interleukin (IL)-33 in the cornea and human corneal epithelial cells (HCECs) exposed to Aspergillus fumigatus (A. fumigatus), and to determine the function of IL-33/ST2/p38 signaling pathway in the immune response of corneal epithelial cells to A. fumigatus infection.
METHODS: The mRNA and protein expression of IL-33 in HCECs and mice corneas were examined by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analysis, respectively. IL-33 expression was also detected in cornea samples from healthy donors and patients with fungal keratitis with immunohistochemistry. The cultured HCECs were treated with inactive A. fumigatus hyphae at various concentrations with or without recombinant human IL-33 protein, soluble recombinant ST2 protein, specific ST2 neutralizing antibody, or the mitogen-activated protein kinase (MAPK) p38 inhibitor SB203580 for evaluation of the expression and activation of IL-33/ST2/p38 signaling in the regulation of proinflammatory cytokines. The production levels of IL-6 and IL-1β were determined by qRT-PCR and enzyme-linked immunosorbent assay (ELISA). The proliferation of HCECs was determined by a Cell Counting Kit-8 (CCK8) assay and cell count.
RESULTS: IL-33 expression levels increased in the corneal tissues of patients with fungal keratitis and in mice corneas of experimental A. fumigatus infection, as well as in HCECs with infection of A. fumigatus. A. fumigatus strongly stimulated HCECs-generated proinflammatory cytokine (IL-6 and IL-1β) production at both the mRNA and protein levels. This production of pro-inflammatory mediators stimulated by A. fumigatus was further stimulated by IL-33 and was prevented by soluble ST2 protein or ST2 neutralizing antibody. Moreover, IL-33 naturally promoted the p38 phosphorylation induced by A. fumigatus, which was suppressed by soluble ST2 protein. The MAPK p38 inhibitor SB203580 also inhibited the A. fumigatus-induced proinflammatory cytokine production. IL-33 administration for 48h and 72h promoted the proliferation of HCECs, which was attenuated by treatment with soluble recombinant human ST2 protein.
CONCLUSION: A. fumigatus elevates IL-33 expression in human and mice corneas and HCECs. Thus, IL-33/ST2/p38 signaling may play an important role in amplifying the immune response of corneal epithelial cells to A. fumigatus infection. Besides, IL-33 promotes the cell proliferation of HCECs via its receptor ST2. These findings suggest a novel autocrine mechanism of amplification of the fungal-induced inflammatory response in the corneal epithelium, highlighting a potential therapeutic target for fungal keratitis. |
| first_indexed | 2024-12-20T11:43:16Z |
| format | Article |
| id | doaj.art-1f3bd7e7d68e4b9c967716acf522a970 |
| institution | Directory Open Access Journal |
| issn | 2222-3959 2227-4898 |
| language | English |
| last_indexed | 2024-12-20T11:43:16Z |
| publishDate | 2019-04-01 |
| publisher | Press of International Journal of Ophthalmology (IJO PRESS) |
| record_format | Article |
| series | International Journal of Ophthalmology |
| spelling | doaj.art-1f3bd7e7d68e4b9c967716acf522a9702022-12-21T19:41:56ZengPress of International Journal of Ophthalmology (IJO PRESS)International Journal of Ophthalmology2222-39592227-48982019-04-0112454955610.18240/ijo.2019.04.04Role of the IL-33/ST2/p38 signaling pathway in the immune response of corneal epithelial cells to Aspergillus fumigatus infectionJia You0Jing Lin1Yi-Fan Zhou2Xu-Dong Peng3Hong He4Cui Li5Guo-Qiang Zhu6Xue-Qi Zhao7Gui-Qiu Zhao8Department of Ophthalmology, the Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, ChinaDepartment of Ophthalmology, the Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, ChinaDepartment of Ophthalmology, the Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, ChinaDepartment of Ophthalmology, the Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, ChinaDepartment of Clinical Laboratory, the Affiliated Hospital of Qingdao University, Qingdao266003, Shandong Province, ChinaDepartment of Ophthalmology, the Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, ChinaDepartment of Ophthalmology, the Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, ChinaDepartment of Ophthalmology, the Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, ChinaDepartment of Ophthalmology, the Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, ChinaAIM: To investigate the expression of interleukin (IL)-33 in the cornea and human corneal epithelial cells (HCECs) exposed to Aspergillus fumigatus (A. fumigatus), and to determine the function of IL-33/ST2/p38 signaling pathway in the immune response of corneal epithelial cells to A. fumigatus infection. METHODS: The mRNA and protein expression of IL-33 in HCECs and mice corneas were examined by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analysis, respectively. IL-33 expression was also detected in cornea samples from healthy donors and patients with fungal keratitis with immunohistochemistry. The cultured HCECs were treated with inactive A. fumigatus hyphae at various concentrations with or without recombinant human IL-33 protein, soluble recombinant ST2 protein, specific ST2 neutralizing antibody, or the mitogen-activated protein kinase (MAPK) p38 inhibitor SB203580 for evaluation of the expression and activation of IL-33/ST2/p38 signaling in the regulation of proinflammatory cytokines. The production levels of IL-6 and IL-1β were determined by qRT-PCR and enzyme-linked immunosorbent assay (ELISA). The proliferation of HCECs was determined by a Cell Counting Kit-8 (CCK8) assay and cell count. RESULTS: IL-33 expression levels increased in the corneal tissues of patients with fungal keratitis and in mice corneas of experimental A. fumigatus infection, as well as in HCECs with infection of A. fumigatus. A. fumigatus strongly stimulated HCECs-generated proinflammatory cytokine (IL-6 and IL-1β) production at both the mRNA and protein levels. This production of pro-inflammatory mediators stimulated by A. fumigatus was further stimulated by IL-33 and was prevented by soluble ST2 protein or ST2 neutralizing antibody. Moreover, IL-33 naturally promoted the p38 phosphorylation induced by A. fumigatus, which was suppressed by soluble ST2 protein. The MAPK p38 inhibitor SB203580 also inhibited the A. fumigatus-induced proinflammatory cytokine production. IL-33 administration for 48h and 72h promoted the proliferation of HCECs, which was attenuated by treatment with soluble recombinant human ST2 protein. CONCLUSION: A. fumigatus elevates IL-33 expression in human and mice corneas and HCECs. Thus, IL-33/ST2/p38 signaling may play an important role in amplifying the immune response of corneal epithelial cells to A. fumigatus infection. Besides, IL-33 promotes the cell proliferation of HCECs via its receptor ST2. These findings suggest a novel autocrine mechanism of amplification of the fungal-induced inflammatory response in the corneal epithelium, highlighting a potential therapeutic target for fungal keratitis.http://www.ijo.cn/en_publish/2019/4/20190404.pdfst2interleukin 33aspergillus fumigatuscorneap38 mitogen-activated protein kinaseproliferation |
| spellingShingle | Jia You Jing Lin Yi-Fan Zhou Xu-Dong Peng Hong He Cui Li Guo-Qiang Zhu Xue-Qi Zhao Gui-Qiu Zhao Role of the IL-33/ST2/p38 signaling pathway in the immune response of corneal epithelial cells to Aspergillus fumigatus infection International Journal of Ophthalmology st2 interleukin 33 aspergillus fumigatus cornea p38 mitogen-activated protein kinase proliferation |
| title | Role of the IL-33/ST2/p38 signaling pathway in the immune response of corneal epithelial cells to Aspergillus fumigatus infection |
| title_full | Role of the IL-33/ST2/p38 signaling pathway in the immune response of corneal epithelial cells to Aspergillus fumigatus infection |
| title_fullStr | Role of the IL-33/ST2/p38 signaling pathway in the immune response of corneal epithelial cells to Aspergillus fumigatus infection |
| title_full_unstemmed | Role of the IL-33/ST2/p38 signaling pathway in the immune response of corneal epithelial cells to Aspergillus fumigatus infection |
| title_short | Role of the IL-33/ST2/p38 signaling pathway in the immune response of corneal epithelial cells to Aspergillus fumigatus infection |
| title_sort | role of the il 33 st2 p38 signaling pathway in the immune response of corneal epithelial cells to aspergillus fumigatus infection |
| topic | st2 interleukin 33 aspergillus fumigatus cornea p38 mitogen-activated protein kinase proliferation |
| url | http://www.ijo.cn/en_publish/2019/4/20190404.pdf |
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