IL-24 PromotesPseudomonas aeruginosaKeratitis in C57BL/6 Mouse Corneas.
The aim of this study was to elucidate the expression and functions of IL-24 in C57BL/6 mouse corneas in response toPseudomonas aeruginosainfection. 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 exacerbatedP. 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 promotesP. aeruginosakeratitis through the suppression of early protective mucosal immunity, culminating in increased severity ofP. aeruginosakeratitis.
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.
Bing X
BX
Ross
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.
Nan
N
Gao
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.
Xinhan
X
Cui
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109.
Theodore J
TJ
Standiford
Eye and Ear, Nose, and Throat Hospital of Fudan University, Xuhui District, Shanghai 200031, China; and.
Jianjiang
J
Xu
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.
Fu-Shin X
FX
Yu
D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D002460:Cell Line; D003315:Cornea / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005408:Flagellin / Q000008:administration & dosage; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D018928:Immunity, Mucosal; D018836:Inflammation Mediators / Q000378:metabolism; D007634:Keratitis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011552:Pseudomonas Infections / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000235:genetics / Q000378:metabolism; D000099180:Interleukin-24
D019138:Antibodies, Blocking; D016207:Cytokines; D005408:Flagellin; D018836:Inflammation Mediators; D034741:RNA, Small Interfering; D000071223:Suppressor of Cytokine Signaling 3 Protein; C431904:Il24 protein, mouse; D000099180:Interleukin-24; C491411:Socs3 protein, mouse