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-reg ulation of proliferation of their progenitors. This study focuses on the ex pression of the neuropoietic cytokines leukemia inhibitory factor (LIF) and its receptor (LIFR) and interleukin 6 (IL-6) and its receptor (IL-GR) in i ntercellular signaling pathways in the olfactory mucosa after target ablati on. Olfactory bulbectomy (OBX) resulted in several transient, early-onset, temporally integrated events that were detected immunohistochemically. Macr ophages infiltrated the olfactory epithelium (OE) by 16 hours post-OBX. LIF expression was up-regulated transiently at 2 days post-OBX, when up-regula ted expression of LIFR also was detected on globose basal cells (GBCs), a s ubpopulation of which are immediate progenitors of olfactory receptor neuro ns. 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 upregulation of expression of LIFR, IL-6, and IL-6R in enshe athing cells by 3 days post-OBX. The mRNAs for LIF/LIFR, IL-6/IL-GR, and th eir common signal-transduction molecule, gp130, in olfactory-nasal mucosa f rom control mice and from 3-day post-OBX mice were detected with reverse tr anscriptase-polymerase chain reaction (RT-PCR). Analysis of Northern blot a nd relative quantitative RT-PCR demonstrated similar temporal patterns of c hanges in relative mRNA levels for both LIF and IL-6, which were up-regulat ed by 16 hours post-OBX and peaked at 2-3 days post-OBX. These data indicat e that LIF from infiltrating macrophages acts as a mitogen for GBCs and tha t LIF from infiltrating macrophages and IL-6 from infiltrating macrophages and ensheathing cells act as repair factors in the ON. (C) 2001 Wiley-Liss, Inc.