fig2

Figure 2. Summary of cellular interactions leading to cutaneous scar formation. When the skin is damaged, an inflammatory response is induced. Initially, resident inflammatory cells (e.g., mast cells and macrophages) in the dermis are activated. These activated cells secrete molecules that stimulate fibroblast activity and promote collagen production and scar tissue deposition. The resident cell-derived mediators, particularly cytokines (and chemokines) as well as lipids, stimulate the recruitment of circulating inflammatory cells (e.g., neutrophils, monocytes, and mast cell precursors) into the tissue. These cells become activated, and in some cases mature (monocytes become macrophages and mast cell precursors become mature mast cells), leading to even higher local levels of mediators that stimulate fibroblast activity and perpetuate scar tissue production. Several types of mediators produced by inflammatory cells have been linked to scar formation, including growth factors (TGF-β1), cytokines/chemokines [interleukin (IL)-6, IL-17, IL-33, MCP-1, SDF-1, OPN], proteases (mast cell chymase/tryptase, neutrophil elastase), lipids (PGE₂), and reactive oxygen species or ROS (H₂O₂)