TNF-α mainly produced by activated monocytes/macrophages and activated T lymphocytes, is a pleiotropic cytokine, which possess a very strong pro-inflammatory response and immunomodulatory property. TNF-α mainly plays a biological effect via cell membrane receptors TNFR1 and TNFR2. TNFR1 mainly mediates TNF-α signal transduction, and TNFR2 only plays a supporting role. Previous studies have shown that TNF-α plays an important role in the process of wound healing[15].
Castagnoli et al[16] studied the expression of TNF-α in hypertrophic scar tissues by using immunohistochemistry method. The results showed that, compared with normal scar, the expression of TNF-α significantly reduced in hypertrophic scar tissues. In recent years, with in-depth study of trauma and repair, results demonstrated that: TNF in hypertrophic scar tissue expression was significantly less than that of the normal scar tissue. In vitro experiments, TNF inhibited fibroblast collagen gene transcription and protein synthesis, simultaneously, lead to increase of collagenase gene transcription, thus, TNF exhibited a great significance in the tissue remodeling[17]. Duncan[18] studies have shown that TNF play a catabolism role in the skin fibrosis. Therefore, the artificial regulation wound tissues of TNF-α levels, and perhaps avoid or minimize the excessive proliferation of scar tissue, thereby reducing their impact on a number of complications. TNF-α acts on skin fibroblast cells in a dose-dependent promotion of fibroblast collagen, mucopolysaccharide, collagenase production. Compared to collagen, the synthesis and catabolism production of collagenase was more than 10-fold[19].
The experimental results also support this view. Here, in this experiment, NIH3T3 cells cultured with a certain concentration of TNF-α, the specificity kinase signal of transduction pathway presented with phosphorylation or protein activation, and the signal pathway was activated, which promoted MMP3 activation, and significantly reduced the expression of type Ⅰ collagen. The effect of TNF-α was certainly inhibited, but not completely eliminated after adding its signal transduction pathway inhibitor Anti-TNFRSF1B. This further proves the role of TNF-α on NIH3T3 activation.
Pathological scars include hypertrophic scars and keloids, the formation mechanisms of which are not yet fully understood. Histologically, abnormal scar mainly present as the repair cells (mainly fibroblasts) and a large number of barriers to proliferation and apoptosis, extracellular matrix disbalance between collagen synthesis and degradation balance, with some of the large number of produced cytokines. These three factors together constitute the biological basis of pathological scar[20]. Thus, by interfering with pro-inflammatory cytokine signal transduction pathways, to observe trends in fibroblast activation and its biological function, explore basic conditions for regulating fibroblast activity, and to search the pro-inflammatory cytokines in the epidural scar tissue formation on fibroblast cells. At the same time, this study provides a theoretical foundation for developing biological materials that can prevent epidural adhesion or establishing sustained release system that interfere pro-inflammatory cytokines.
