title: NF-κB-dependent role for cold-inducible RNA binding protein in regulating interleukin 1β.
abstract: The cold inducible RNA binding protein (CIRBP) responds to a wide array of cellular stresses, including short wavelength ultraviolet light (UVC), at the transcriptional and post-translational level. CIRBP can bind the 3'untranslated region of specific transcripts to stabilize them and facilitate their transport to ribosomes for translation. Here we used RNA interference and oligonucleotide microarrays to identify potential downstream targets of CIRBP induced in response to UVC. Twenty eight transcripts were statistically increased in response to UVC and these exhibited a typical UVC response. Only 5 of the 28 UVC-induced transcripts exhibited a CIRBP-dependent pattern of expression. Surprisingly, 3 of the 5 transcripts (IL1B, IL8 and TNFAIP6) encoded proteins important in inflammation with IL-1β apparently contributing to IL8 and TNFAIP6 expression in an autocrine fashion. UVC-induced IL1B expression could be inhibited by pharmacological inhibition of NFκB suggesting that CIRBP was affecting NF-κB signaling as opposed to IL1B mRNA stability directly. Bacterial lipopolysaccharide (LPS) was used as an activator of NF-κB to further study the potential link between CIRBP and NFκB. Transfection of siRNAs against CIRBP reduced the extent of the LPS-induced phosphorylation of IκBα, NF-κB DNA binding activity and IL-1β expression. The present work firmly establishes a novel link between CIRBP and NF-κB signaling in response to agents with diverse modes of action. These results have potential implications for disease states associated with inflammation.
authors: Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, Canada.
authors: Christian
authors: C
authors: Brochu
authors: Miguel A
authors: MA
authors: Cabrita
authors: Brian D
authors: BD
authors: Melanson
authors: Jeffrey D
authors: JD
authors: Hamill
authors: Rosanna
authors: R
authors: Lau
authors: M A Christine
authors: MA
authors: Pratt
authors: Bruce C
authors: BC
authors: McKay
mesh_terms: D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology; D003080:Cold Temperature; D005347:Fibroblasts; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000276:immunology; D053583:Interleukin-1beta / Q000235:genetics* / Q000276:immunology; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics* / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D061251:Primary Cell Culture; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: C491390:CIRBP protein, human; D015815:Cell Adhesion Molecules; D020672:I-kappa B Proteins; D053583:Interleukin-1beta; D016209:Interleukin-8; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C072273:TNFAIP6 protein, human; D000072000:NF-KappaB Inhibitor alpha