The CXC chemokine cCAF stimulates precocious deposition of ECM molecules by wound fibroblasts, accelerating development of granulation tissue

Background: During wound repair, fibroblasts orchestrate replacement of the provisional matrix formed during clotting with tenasin, cellular fibronectin and collagen III. These, in turn, are critical for migration of endothelial ells, keratinocytes and additional fibroblasts into the wound site. Fibroblasts are also important in the deposition of collagen I during scar formation. The CXC chemokine chicken Chemotactic and Angiogenic Fa or (cCAF), is highly expressed by fibroblasts after wounding and during development of the granulation tissue, especially in areas where extracellular matrix (ECM) is abundant. We hypothesized that CAF stimulates fibroblasts to produce these matrix molecules. Result : Here we show that this chemokine can stimulate precocious deposition of tenascin, fibronectin and collagen I, but no collagen III. Studies in culture and in vivo show that tenasin stimulation can also be achieved by the N-terminal 15 aas of he protein and occurs at the level of gene expression. In contrast, stimulation of fibronectin and collagen I both require the entire molecule and do no involve changes in gene expression. Fibronectin accumulation appears to be linked to tenascin production, and collagen I to decreased MMP-1 levels. In addition, CAF is chemotactic for fibroblasts and accelerates their migration. Conclusions: These previously unknown functions for chemokines suggest that cCAF, the chicken orthologue of human IL-8, enhances healing by rapidly chemoattracting fibroblasts into the wound site and stimulating them to produce ECM molecules, leading to precocious development of granulation tissue. This acceleration of he repair process may have important application to healing of impaired wounds.