IL-1 Exposure Significantly increases gene expression of BDNF, NTF3 and NRP2 as well as NGF Production in Human Annulus Cells

ABSTRACT: Although the degenerating disc is considered to be the key source of pain in patients with low back pain, the relationship between disc cells, nerves, and pain production is poorly understood. Neurotrophins are signaling molecules involved in the survival, differentiation, migration, and neurite outgrowth of central and peripheral neurons. Neurotrophins are now known to be expressed in non-neuronal tissues, including the intervertebral disc. We hypothesize that the inflammatory cytokine interleukin-1 (IL-1beta), which is produced by disc cells during degeneration, is a key element in the cascade of events involving neurotrophins. To test this, we used an in vitro experimental design which challenged 3D-cultured human annulus cells with IL-1beta and utilized microarray analysis to evaluate neurotrophin- and nerve-related gene expression profiles in treated vs. control cells. Analysis of nerve growth factor levels in conditioned media was also performed. Findings presented here support the hypothesis that proinflammatory cytokines (which are produced by disc cells during degeneration) are involved with a significant increase in the expression of neurotrophins and other nerve-related genes. Findings expand previous data on expression of neurotrophins in the degenerating disc, and provide the first documentation of expression of neurotrophin 3 and neuropilin 2. These results have direct translational relevance because they address the primary clinical issue with disc degeneration (low back pain) and open the possibility of novel analgesic therapies based on development of specific small-molecular antagonists to neurotrophins.

ORGANISM(S): Homo sapiens

PROVIDER: GSE27494 | GEO | 2012/06/27

SECONDARY ACCESSION(S): PRJNA138423

REPOSITORIES: GEO