title: HuR/ELAVL1 RNA binding protein modulates interleukin-8 induction by muco-active ribotoxin deoxynivalenol.
abstract: HuR/Elav-like RNA binding protein 1 (ELAVL1) positively regulates mRNA stability of AU-rich elements (ARE)-containing transcript such as pro-inflammatory cytokines. Ribotoxic stresses can trigger the production of pro-inflammatory mediators by enhancing mRNA stability and the transcriptional activity. We investigated the effects of ribotoxin deoxynivalenol (DON) on HuR translocation and its involvement in the regulation of the pro-inflammatory interleukin-8 (IL-8) mRNA stability. Exposure to the muco-active DON induced nuclear export of both endogenous and exogenous HuR RNA binding protein in human intestinal epithelial cells. Moreover, the interference with HuR protein production suppressed ribotoxic DON-induced IL-8 secretion and its mRNA stability. Cytoplasmic HuR protein interacted with IL-8 mRNA and the complex stabilization was due to the presence of 3'-untranslated region of the transcript. Partly in terms of IL-8-modulating transcription factors, HuR protein was demonstrated to be positively and negatively associated with DON-induced early growth response gene 1 (EGR-1) and activating transcription factor 3 (ATF3), respectively. HuR was a critical mechanistic link between ribotoxic stress and the pro-inflammatory cytokine production, and may have a broader functional significance with regard to mucosal insults since ribotoxic stress responses are also produced upon interactions with the diverse environment of gut.
authors: Department of Microbiology and Immunology and Medical Research Institute, Pusan National University School of Medicine, Yangsan, 626-813, Republic of Korea.
authors: Hye Jin
authors: HJ
authors: Choi
authors: Hyun
authors: H
authors: Yang
authors: Seong Hwan
authors: SH
authors: Park
authors: Yuseok
authors: Y
authors: Moon
mesh_terms: D000954:Antigens, Surface / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D006801:Humans; D016209:Interleukin-8 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D020871:RNA Stability / Q000187:drug effects / Q000502:physiology; D016601:RNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D012270:Ribosomes / Q000187:drug effects / Q000378:metabolism*; D014255:Trichothecenes / Q000633:toxicity*
chemical_list: D000954:Antigens, Surface; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D016209:Interleukin-8; D016601:RNA-Binding Proteins; D014255:Trichothecenes; C007262:deoxynivalenol