Leukemia inhibitory factor, interleukin-6, and their receptors are expressed transiently in the olfactory mucosa after target ablation.
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.
Nan
B
B
Sanders-Brown Center on Aging, University of Kentucky College of Medicine, Lexington, Kentucky 40536, USA.
Getchell
M L
ML
Partin
J V
JV
Getchell
T V
TV
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
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