Influence of injury and cytokines on synthesis of monocyte chemoattractantprotein-1 mRNA in peripheral nervous tissue

The signals and the source of the signals for monocyte/macrophage entry int o the injured peripheral nervous tissue are not yet defined. This study was undertaken to determine the distribution of the chemokine monocyte chemoat tractant protein-1 mRNA in injured rat and mouse nerves and to investigate the mechanisms that regulate its synthesis in rat Schwann cells. Results fr om RNase protection assays showed that, following sciatic nerve transection in rats, mRNA for monocyte chemoattractant protein-1 was induced at the si te of lesion within 3 h of surgery and in more distal segments from 24 h fo r at least 8 days. In cultured Schwann cells, tumour necrosis factor-alpha but not interleukin-1 beta, interleukin-6, transforming growth factor-beta1 , 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 treat ed with tumour necrosis factor-alpha was reduced by inhibitors of nuclear f actor-kappaB and the p38 mitogen-activated protein kinase. In mice that lac k the two receptors for tumour necrosis factor, the message for JE, a murin e 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 contr ol mice. Tumor necrosis factor-alpha is the only cytokine that was shown to induce monocyte chemoattractant protein-1 mRNA in cultured Schwann cells a nd is one of the factors that regulate the synthesis of monocyte chemoattra ctant protein-1 in injured nerves.