Proteins in Human Corneal Epithelial Cells Fight Pathogens
(HealthDay News) – Epithelial cytokeratins constitutively produce cytoprotective antimicrobial peptides and serve as an innate defense mechanism in human corneal epithelial cells, according to a study published online Sept 24 in the Journal of Clinical Investigation.
Connie Tam, PhD, from the School of Optometry at the University of California in Berkeley, and colleagues examined the defense mechanisms in human corneal epithelial cells during healthy conditions. Cells were systematically fractionated and mass spectrometry was performed.
In the bactericidal lysate fractions, the researchers identified glycine-rich C-terminal fragments derived from human cytokeratin 6A. Coil structures with low α-helical content were exhibited in these keratin-derived antimicrobial peptides (KDAMPs). Rapid bactericidal activity against multiple peptides was demonstrated by synthetic analogs of these KDAMPs and they protected epithelial cells against bacterial virulence mechanisms. No bactericidal activity was seen with a scrambled peptide. Glycine-alanine substitutions reduced the bactericidal activity of a specific KDAMP. KDAMP activity was unaffected by peptide charge or physiological salt concentrations but did involve bacterial binding and permeabilization. Cytokeratin 6A knockdown reduced the bactericidal activity of epithelial cell lysates in vitro and correlated with an in vivo increase in susceptibility of murine corneas to bacterial adherence.
"These data suggest that epithelial cytokeratins function as endogenous antimicrobial peptides in the host defense against infection and that keratin-derived antimicrobials may serve as effective therapeutic agents," the authors write.
The authors of the study have submitted this data as part of a patent application.