Abstract

Chemokines are inflammatory mediators with effects on diverse processes associated with the immune response. Some of the proteins belonging to the CXC chemokine subfamily, one of four groups in the family, possess inherent antibacterial activity against a wide range of bacteria. The CXC chemokine interleukin-8 (IL-8) has not been ascribed any direct antibacterial activity, but the fact that several of the amino acids in the carboxy-terminal part of the protein are identical or similar to those in a bactericidal cecropin-like peptide [Hp(2-20)] from Helicobacter pylori suggests that processing of the cytokine might generate peptide fragments with antibacterial properties. Synthetic peptides representing the carboxy-terminal part of IL-8 were investigated for antibacterial activities. These fragments possessed an antibacterial activity absent in the full-length IL-8. The antibacterial effects were reduced at increasing salt concentrations whereas the activity was increased when the pH was lowered. The IL-8-derived peptide shared structural similarity with and was also functionally additive to the Hp(2-20) peptide. The IL-8-derived peptide lacked the proinflammatory effects of the full-length protein. We also showed that acid hydrolysis of IL-8 generated a major peptide fragment corresponding to the antibacterial carboxyl terminus of the protein. The results presented are of special interest when put in the context of the suggested importance of antimicrobial peptides for microbial colonization of the gastric mucosa.