title: Cell type- and stimulus-specific mechanisms for post-transcriptional control of neutrophil chemokine gene expression.
abstract: mRNAs encoding inflammatory chemokines that recruit neutrophils frequently exhibit short half-lives that serve to limit their expression under inappropriate conditions but are often prolonged to ensure adequate levels during inflammatory response. Extracellular stimuli that modulate the stability of such mRNAs may be the same as the transcriptional activator, as is the case with TLR ligands, or may cooperate with independent transcriptional stimuli, as with IL-17, which extends the half-life of TNF-induced transcripts. These different stimuli engage independent signaling pathways that target different instability mechanisms distinguished by dependence on different regulatory nucleotide sequence motifs within the 3'UTRs, which involve that action of different mRNA-binding proteins. The selective use of these pathways by different stimuli and in distinct cell populations provides the potential for tailoring of chemokine expression patterns to meet specific needs in different pathophysiologic circumstances.
authors.affiliation: Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195-0001, USA. hamiltt@ccf.org
authors.forename: Thomas
authors.initials: T
authors.lastname: Hamilton
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Li
authors.forename: Michael
authors.initials: M
authors.lastname: Novotny
authors.forename: Paul G
authors.initials: PG
authors.lastname: Pavicic
authors.forename: Shyamasree
authors.initials: S
authors.lastname: Datta
authors.forename: Chenyang
authors.initials: C
authors.lastname: Zhao
authors.forename: Justin
authors.initials: J
authors.lastname: Hartupee
authors.forename: Dongxu
authors.initials: D
authors.lastname: Sun
mesh_terms: D000818:Animals; D018925:Chemokines / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism; D051816:Tristetraprolin / Q000378:metabolism
chemical_list: D018925:Chemokines; D020381:Interleukin-17; D012333:RNA, Messenger; D051193:Toll-Like Receptors; D051816:Tristetraprolin