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IL-24 Promotes Pseudomonas aeruginosa Keratitis in C57BL/6 Mouse Corneas.
J Immunol 2017; 198(9):3536-3547JI

Abstract

The aim of this study was to elucidate the expression and functions of IL-24 in C57BL/6 mouse corneas in response to Pseudomonas aeruginosa infection. Among IL-20R cytokines, only IL-24 was induced at both mRNA and protein levels by infection at early time points. The upregulation of IL-24 was dampened by flagellin pretreatment, which protects the corneas from microbial infection. Time course studies revealed bimodal early and later peaks of IL-24 expression, a pattern shared with suppressor of cytokine signaling (SOCS)3 but not IL-1β or IL-6. Silencing of IL-24 enhanced S100A8/A9 expression and suppressed SOCS3, IL-1β, IL-1RN, and matrix metalloproteinase 13 expression at 6 h postinfection. Downregulation of the IL-24 signaling pathway significantly reduced the severity of keratitis, whereas rIL-24 exacerbated P. aeruginosa-mediated tissue destruction. In vitro, rIL-1β induced the expression of SOCS3, IL-24, IL-1β, and IL-6 in primary cultured human corneal epithelial cells. rIL-24, alternatively, stimulated the expression of SOCS3, but not the others. In conclusion, IL-24 promotes P. aeruginosa keratitis through the suppression of early protective mucosal immunity, culminating in increased severity of P. aeruginosa keratitis.

Authors+Show Affiliations

Department of Ophthalmology, Wayne State University School of Medicine, Detroit, MI 48201. Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI 48201.Department of Ophthalmology, Wayne State University School of Medicine, Detroit, MI 48201. Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI 48201.Department of Ophthalmology, Wayne State University School of Medicine, Detroit, MI 48201. Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI 48201. Eye and Ear, Nose, and Throat Hospital of Fudan University, Xuhui District, Shanghai 200031, China; and.Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109.Eye and Ear, Nose, and Throat Hospital of Fudan University, Xuhui District, Shanghai 200031, China; and.Department of Ophthalmology, Wayne State University School of Medicine, Detroit, MI 48201; av3899@wayne.edu. Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI 48201.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

28330899

Citation

Ross, Bing X., et al. "IL-24 Promotes Pseudomonas Aeruginosa Keratitis in C57BL/6 Mouse Corneas." Journal of Immunology (Baltimore, Md. : 1950), vol. 198, no. 9, 2017, pp. 3536-3547.
Ross BX, Gao N, Cui X, et al. IL-24 Promotes Pseudomonas aeruginosa Keratitis in C57BL/6 Mouse Corneas. J Immunol. 2017;198(9):3536-3547.
Ross, B. X., Gao, N., Cui, X., Standiford, T. J., Xu, J., & Yu, F. X. (2017). IL-24 Promotes Pseudomonas aeruginosa Keratitis in C57BL/6 Mouse Corneas. Journal of Immunology (Baltimore, Md. : 1950), 198(9), pp. 3536-3547. doi:10.4049/jimmunol.1602087.
Ross BX, et al. IL-24 Promotes Pseudomonas Aeruginosa Keratitis in C57BL/6 Mouse Corneas. J Immunol. 2017 05 1;198(9):3536-3547. PubMed PMID: 28330899.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - IL-24 Promotes Pseudomonas aeruginosa Keratitis in C57BL/6 Mouse Corneas. AU - Ross,Bing X, AU - Gao,Nan, AU - Cui,Xinhan, AU - Standiford,Theodore J, AU - Xu,Jianjiang, AU - Yu,Fu-Shin X, Y1 - 2017/03/22/ PY - 2016/12/13/received PY - 2017/02/27/accepted PY - 2017/3/24/pubmed PY - 2017/5/2/medline PY - 2017/3/24/entrez SP - 3536 EP - 3547 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 198 IS - 9 N2 - The aim of this study was to elucidate the expression and functions of IL-24 in C57BL/6 mouse corneas in response to Pseudomonas aeruginosa infection. Among IL-20R cytokines, only IL-24 was induced at both mRNA and protein levels by infection at early time points. The upregulation of IL-24 was dampened by flagellin pretreatment, which protects the corneas from microbial infection. Time course studies revealed bimodal early and later peaks of IL-24 expression, a pattern shared with suppressor of cytokine signaling (SOCS)3 but not IL-1β or IL-6. Silencing of IL-24 enhanced S100A8/A9 expression and suppressed SOCS3, IL-1β, IL-1RN, and matrix metalloproteinase 13 expression at 6 h postinfection. Downregulation of the IL-24 signaling pathway significantly reduced the severity of keratitis, whereas rIL-24 exacerbated P. aeruginosa-mediated tissue destruction. In vitro, rIL-1β induced the expression of SOCS3, IL-24, IL-1β, and IL-6 in primary cultured human corneal epithelial cells. rIL-24, alternatively, stimulated the expression of SOCS3, but not the others. In conclusion, IL-24 promotes P. aeruginosa keratitis through the suppression of early protective mucosal immunity, culminating in increased severity of P. aeruginosa keratitis. SN - 1550-6606 UR - https://www.unboundmedicine.com/medline/citation/28330899/IL_24_Promotes_Pseudomonas_aeruginosa_Keratitis_in_C57BL/6_Mouse_Corneas_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=28330899 DB - PRIME DP - Unbound Medicine ER -