title: A role for IL-10 in the transcriptional regulation of Roquin-1.
abstract: Roquin-1, a RING finger E3 ubiquitin ligase, functions as a modulator of inflammation; however, nothing is known about how Rc3h1 expression is regulated. Here, we describe an opposing relationship between Roquin-1 and the IL-17 proinflammatory cytokine by demonstrating that enforced expression of Rc3h1 restricts Il17a expression, and that exposure of T cells to IL-10, a cytokine with immunosuppressive activity, increases Rc3h1 expression. Luciferase reporter assays conducted using eight transcription factor plasmids (STAT1, STAT3, STAT5, GATA2, c-Rel, IKZF1, IKZF2, and IKZF3) demonstrated that STAT1, STAT3, GATA2, and c-Rel increased Rc3h1 promoter activity, whereas IKZF2 decreased activity. Gene expression of those five transcription factors increased in T cells exposed to IL-10. Transcription factor-specific siRNAs suppressed the IL-10 effect on Rc3h1 transcription. These findings identify a role for IL-10 in regulating Rc3h1 transcription, and they have implications for understanding how Roquin-1 controls the immune response.
authors: Department of Diagnostic and Biomedical Sciences, School of Dentistry, The University of Texas Health Science Center at Houston, Houston, TX 77054, USA.
authors: Jeremy S
authors: JS
authors: Schaefer
authors: Department of Diagnostic and Biomedical Sciences, School of Dentistry, The University of Texas Health Science Center at Houston, Houston, TX 77054, USA.
authors: Dina
authors: D
authors: Montufar-Solis
authors: Department of Diagnostic and Biomedical Sciences, School of Dentistry, The University of Texas Health Science Center at Houston, Houston, TX 77054, USA. Electronic address: john.r.klein@uth.tmc.edu.
authors: John R
authors: JR
authors: Klein
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: C556062:IL10 protein, mouse; C098680:Il17a protein, mouse; D020381:Interleukin-17; D014157:Transcription Factors; D016753:Interleukin-10; C501406:Rc3h1 protein, mouse; D044767:Ubiquitin-Protein Ligases
keywords: Cytokine; Gene expression; IL-10; Luciferase; Promoter; Transcription factor; siRNA