Defensins

The expression of human ß-defensin-1 (hBD-1), the first isolated human ß-defensin, is constitutive in epidermal keratinocytes and shows antimicrobial activity against predominantly Gramnegative bacteria such as Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa) [3, 20]. The constitutive expression of hBD-1 in the suprabasal layers of the epidermis suggests that it contributes to the innate resistance of the skin to Gram-negative infections.

The second human ß-defensin, hBD-2, was originally isolated from the desquamated scales of psoriatic skin [26]. Several data suggest a complex role for hBD-2 in cutaneous host defense. It has a microbicidal effect against various microorganisms, such as E. coli and P. aeruginosa, S. aureus or Streptococcus pyogenes (St. pyogenes) [64], but also acts as a chemoattrac-tant for immature dendritic cells and neutro-phils, and induces the migration of memory T cells. The expression of hBD-2 in vivo is localized to the upper layer of the epidermis and the stratum corneum. hBD-2 was also found in the intercellular space indicating that the lipid "permeability" barrier of the skin contains antimicrobial substances [57]. In correlation with the localization of hBD-2 in the more differentiated suprabasal layers of epidermis, differentiationregulated expression of hBD-2 was also demon-13 strated in primary keratinocytes [3, 44]. Furthermore, the abundant expression of hBD-2 in inflamed and in infected skin parallels with the finding that its expression is induced by Grampositive (E. coli, P. aeruginosa and Propionibac-terium acnes) and Gram-negative (S. aureus or St. pyogenes) bacteria and also by C. albicans in cultured keratinocytes and in reconstructed human epidermis [9, 11, 13, 26, 28, 54].

hBD-2 binds specifically to CC chemokine receptor 6 (CCR6) and mediates the chemotaxis of CCR6+ cells such as dendritic cells and T lymphocytes, which have an important role in the adaptive immune response against pathogens [77, 80]. The chemotactic activity of hBD-2 for immature dendritic cells and memory T cells, however, requires much lower concentrations than its antimicrobial activity [44]. hBD-2 also induces the maturation of dendritic cells in a TLR4-dependent manner [7]. In vivo, the secretion of hBD-2 by keratinocytes activates dendritic cells, inducing their migration from the skin into local lymphoid organs, leading to the generation of the cellular immune response through the activation of antigen-specific T cells [39]. Thus, hBD-2 plays multiple roles in cutaneous host defense: (1) it provides the first line of defense against infection by acting as a "natural antibiotic" against sensitive pathogens; and (2) it plays a key role in the initiation of adaptive immune responses against infections by directing the migration of dendritic cells and/or T cells and inducing DC maturation. Taken together, hBD-2 provides a link between the innate and adaptive immune responses during skin infections.

hBD-3 has been cloned from keratinocytes and it shows a broad spectrum of antimicrobial activity against Gram-negative and Grampositive bacteria including multi-resistant bacteria. Its expression in keratinocytes is induced by PAMPs, inflammatory mediators such as TNF-a, IL-1ß, IFN-y, and by the state of differentiation [27, 28].

Similarly to hBD-2 and -3, the production of hBD-4 in keratinocytes is inducible by inflammatory stimuli, PAMPs or differentiation [28]. Synthetic hBD-4 revealed antimicrobial activity against P. aeruginosa and Staphylococcus carno-sus, implicating a role for this peptide in the innate epidermal defense against bacterial infections.

How To Reduce Acne Scarring

How To Reduce Acne Scarring

Acne is a name that is famous in its own right, but for all of the wrong reasons. Most teenagers know, and dread, the very word, as it so prevalently wrecks havoc on their faces throughout their adolescent years.

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