Fig. 5
Post-translational modifications affect the biological activity of CXCL8. Natural CXCL8 has been identified as a partially citrullinated protein and as multiple NH2-terminally truncated proteoforms (green, red, and gray boxes). Citrullination of CXCL8 on Arg5 significantly reduces its biological activity whereas removal of 5–8 amino acids significantly potentiates the activity of CXCL8 up to almost 30-fold, compared to CXCL8(1–77). Moreover, due to induction of increased neutrophil migration and activation, additional proteases are released which again enhance the proteolytic activation of CXCL8 (positive feedback loop). Further proteolytic cleavage in the ELR motif and nitration have not been reported on natural CXCL8 (yellow boxes) but CXCL8(10–77) could be generated after incubation of CXCL8 with MMP-12. Cleavage in the ELR motif or nitration reduce or abolish the activity of CXCL8 in vitro
