title: Leukemia inhibitory factor, interleukin-6, and their receptors are expressed transiently in the olfactory mucosa after target ablation.
abstract: Removal of the synaptic targets of olfactory receptor neurons by olfactory bulb ablation results in apoptosis of olfactory receptor neurons and up-regulation of proliferation of their progenitors. This study focuses on the expression of the neuropoietic cytokines leukemia inhibitory factor (LIF) and its receptor (LIFR) and interleukin 6 (IL-6) and its receptor (IL-6R) in intercellular signaling pathways in the olfactory mucosa after target ablation. Olfactory bulbectomy (OBX) resulted in several transient, early-onset, temporally integrated events that were detected immunohistochemically. Macrophages infiltrated the olfactory epithelium (OE) by 16 hours post-OBX. LIF expression was up-regulated transiently at 2 days post-OBX, when up-regulated expression of LIFR also was detected on globose basal cells (GBCs), a subpopulation of which are immediate progenitors of olfactory receptor neurons. GBC proliferation peaked at 3--4 days post-OBX. In the olfactory nerve (ON), LIF-positive and IL-6-positive macrophage infiltration was followed by the transient up-regulation of expression of LIFR, IL-6, and IL-6R in ensheathing cells by 3 days post-OBX. The mRNAs for LIF/LIFR, IL-6/IL-6R, and their common signal-transduction molecule, gp130, in olfactory-nasal mucosa from control mice and from 3-day post-OBX mice were detected with reverse transcriptase-polymerase chain reaction (RT-PCR). Analysis of Northern blot and relative quantitative RT-PCR demonstrated similar temporal patterns of changes in relative mRNA levels for both LIF and IL-6, which were up-regulated by 16 hours post-OBX and peaked at 2--3 days post-OBX. These data indicate that LIF from infiltrating macrophages acts as a mitogen for GBCs and that LIF from infiltrating macrophages and IL-6 from infiltrating macrophages and ensheathing cells act as repair factors in the ON.
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky College of Medicine, Lexington, Kentucky 40536, USA.
authors.forename: B
authors.initials: B
authors.lastname: Nan
authors.forename: M L
authors.initials: ML
authors.lastname: Getchell
authors.forename: J V
authors.initials: JV
authors.lastname: Partin
authors.forename: T V
authors.initials: TV
authors.lastname: Getchell
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D002455:Cell Division / Q000502:physiology; D003714:Denervation; D015870:Gene Expression / Q000276:immunology; D006131:Growth Inhibitors / Q000032:analysis / Q000235:genetics*; D015850:Interleukin-6 / Q000032:analysis / Q000235:genetics*; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008222:Lymphokines / Q000032:analysis / Q000235:genetics*; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL / Q000502:physiology*; D009416:Nerve Regeneration / Q000276:immunology; D009830:Olfactory Bulb / Q000737:chemistry / Q000502:physiology / Q000601:surgery; D009831:Olfactory Mucosa / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D018121:Receptors, Cytokine / Q000032:analysis / Q000235:genetics*; D019947:Receptors, Interleukin-6 / Q000032:analysis / Q000235:genetics*; D053606:Receptors, OSM-LIF; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology / Q000502:physiology
chemical_list: D006131:Growth Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; C507838:Lif protein, mouse; C507841:Lifr protein, mouse; D008222:Lymphokines; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D019947:Receptors, Interleukin-6; D053606:Receptors, OSM-LIF