Figure 2.

Pathways and effects for chemerin, chemerin peptides and ChemR23 in inflammation. (i) Pro-chemerin is cleaved by proteolytic enzymes released upon neutrophil degranulation at the inflammatory site, generating the potent chemoattractant chemerin 35, 36, 38. (ii) Chemerin engages ChemR23 on circulating monocytes and tissue macrophages (MФ), recruiting these cells to the inflamed site [38]. (iii) Activated MФs release proteolytic enzymes to eliminate and digest invading organisms; however, they also serve to cleave chemerin to generate (iv) potent anti-inflammatory peptides, capable of engaging ChemR23 to reprogram activated monocyte-derived MФs toward an anti-inflammatory and/or proresolving phenotype. (v) The expression of proinflammatory mediators by MФs is repressed and anti-inflammatory and wound repair cytokines, including interleukin (IL)-10 and tumor growth factor (TGF)-β are induced. Chemerin peptides (e.g. C15; see Fig. 1) promote efficient clearance of pathogens (vi) and apoptotic cells (vii) at the inflammatory site, thereby aiding restoration of normal tissue structure and function.