Expression of Leukemia Inhibitory Factor in Human Nerve following Injury

Abstract

In animal models of peripheral nerve injury, leukemia inhibitory factor (LIF) is normally expressed at very low levels. Following nerve injury, its expression is rapidly increased in the nerve at the injury site and promotes both sensory and motor neuron survival. Once normal nerve function is restored, LIF expression returns to negligible levels. For this reason, LIF is considered to be a peripheral nerve trauma factor. We wished to determine whether LIF is also upregulated in human nerves following trauma and whether it is expressed in neuromas of varying age. Immunohistochemical staining for the presence of LIF was performed on injured and control human nerves from a number of subjects. Results demonstrate that LIF expression is increased in nerves within hours of injury and, in the case of neuroma formation, can persist for several years. LIF immunoreactivity was consistently found in Schwann cells, in peripheral nerve axons, and, at stages when an inflammatory response was present, also in neutrophils, mast cells, macrophages, and blood vessel walls. The level of staining within the connective tissue of injured nerves was elevated compared to control nerves, which may be due to the presence of LIF bound to the soluble secreted form of the LIF receptor. Whether the continued expression of LIF is unhealed injured nerves promotes the development of neuromas remains to be resolved.

Expression of insulin‐like growth factor‐II and leukemia inhibitory factor antibody immunostaining on the ionized calcium‐binding adaptor molecule 1‐positive microglias in the spinal cord of amyotrophic lateral sclerosis patients

“…LIF is a stable compound that promotes neuronal survival in animal models of neurodegeneration 37 . It was reported that, although LIF is normally expressed at very low levels, its expression is rapidly increased in the nerve following injury, and that it promotes both sensory and motor neuron survival 38 . The abundant expression of LIF receptors on motor neurons and the increase of retrograde axonal transport of LIF by motor neurons following peripheral nerve injury were reported 39 .…”

Triple Knock-Out ofCNTF,LIF, andCT-1Defines Cooperative and Distinct Roles of these Neurotrophic Factors for Motoneuron Maintenance and Function

“…Furthermore, it can induce several neuropeptides through alteration of neuronal gene expression (Patterson and Nawa, 1993) known to be involved in the response of neural tissue to injury (Sun et al, 1996). LIF is retrogradely transported to the cell body of spinal motoneurons and rapidly upregulated when nerve injury occurs (Curtis et al, 1994;Dowsing et al, 2001). LIF also protects facial motoneurons from axotomyinduced cell death (Hughes et al, 1993) and promotes regeneration after nerve injury (Tham et al, 1997;Cafferty et al, 2001).…”

Blood vitronectin is a major activator of LIF and IL-6 in the brain through integrin–FAK and uPAR signaling

“…LIF is expressed at very low levels throughout the body, but increases following brain injury (Banner et al, 1997) and stroke . Its expression in injured peripheral nerves is decreased again after repair (Dowsing et al, 2001), perhaps coincident with re-establishment of vascular integrity. The mechanisms regulating LIF expression are not well understood, but may include stimulation by IL-1β, possibly through mRNA stabilization (Carlson et al, 1996).…”