Influence of injury and cytokines on synthesis of monocyte chemoattractant protein-1 mRNA in peripheral nervous tissue.

Abstract

The signals and the source of the signals for monocyte/macrophage entry into the injured peripheral nervous tissue are not yet defined. This study was undertaken to determine the distribution of the chemokine monocyte chemoattractant protein-1 mRNA in injured rat and mouse nerves and to investigate the mechanisms that regulate its synthesis in rat Schwann cells. Results from RNase protection assays showed that, following sciatic nerve transection in rats, mRNA for monocyte chemoattractant protein-1 was induced at the site of lesion within 3 h of surgery and in more distal segments from 24 h for at least 8 days. In cultured Schwann cells, tumour necrosis factor-alpha but not interleukin-1 beta, interleukin-6, transforming growth factor-beta 1, platelet-derived growth factor-BB or nerve growth factor induced monocyte chemoattractant protein-1 mRNA in a time- and dose-dependent fashion. The induction of monocyte chemoattractant protein-1 mRNA in Schwann cells treated with tumour necrosis factor-alpha was reduced by inhibitors of nuclear factor-kappa B and the p38 mitogen-activated protein kinase. In mice that lack the two receptors for tumour necrosis factor, the message for JE, a murine homologue of monocyte chemoattractant protein-1, was still induced within 6 h of injury at the lesion site. However, in more distal segments 4 days after transection the concentration of JE mRNA was lower than that of control mice. Tumor necrosis factor-alpha is the only cytokine that was shown to induce monocyte chemoattractant protein-1 mRNA in cultured Schwann cells and is one of the factors that regulate the synthesis of monocyte chemoattractant protein-1 in injured nerves.