Sebocytes express functional cathelicidin antimicrobial peptides and can act to kill Propionibacterium acnes.

Sebocytes express functional cathelicidin antimicrobial peptides and can act to kill Propionibacterium acnes

Lee DY, Yamasaki K, Rudsil J et al.

J Invest Dermatol, 2008, 128, 1863-1866

There are four pathogenic features of acne, namely increased sebum production, ductal hypercornification, inflammation and increased bacterial activity. How these factors interplay with each other to cause an acne lesion has been a much researched area, and a trigger for an acne lesion remains to be identified. The role of bacteria has been much debated and its contribution to acne pathogenesis has varied from initiation of all stages of acne to just being involved in inflammation.

Sebum may play a role in moisturising the skin surface and may also have a role in protecting against bacterial infections. B-defensins, a family of antimicrobial peptides, have recently been detected in the pilosebaceous unit and are known to be expressed by keratinocytes. Cathelicidins are another family of antimicrobial peptides essential for the protection of skin and are relevant in preventing skin infection in atopic dermatitis [1]. They have synergistic activity with b-defensins. These investigators determined whether cathelicidins are also produced by the pilosebaceous unit.

Cathelicidins are expressed as an inactive protein, hCAP18 that is proteolytically cleaved to peptides such as LL-37, which protects the host cell from infection. This work shows that the precursor hCAP18 was detected in isolated human sebaceous glands dissected from normal scalp skin and measured by reverse transcriptase-PCR. The active cathelicidin protein was then detected in sebaceous glands using the anti-LL-37 immunoglobulin and by western blot analysis. In vitro, mRNA for hCAP18 was detected in a transfected sebocyte cell line SZ95 and its expression was induced by 1,25-dihydroxyvitamin [D.sub.3] and by P. acnes culture supernatant. The presence of cathelicidin protein was also shown by immunofluorescence. In a separate experiment, synthetic LL-37 was shown to kill 100% of S. aureus and P. acnes. In combination with another antimicrobial peptide, psoriasin, LL-37 was even more effective against P. acnes.

This work has two important findings. First, that cathelicidin is expressed by sebocytes and works synergistically with other antimicrobial peptides to effectively kill P. acnes cultures that are known to colonise the pilosebaceous duct. Secondly, that expression of the inactive precursor protein hCAP18 is influenced by vitamin D, suggesting a potential novel role for vitamin D in the defence of the follicle.

Reference

[1.] Ong Py, Ohtake T, Brandt C et al. Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N Engl J Med, 2002, 347, 1151-1160.