Dynamic alteration of human β-defensin 2 localization from cytoplasm to intercellular space in psoriatic skin

Abstract

Defensins are cationic antimicrobial peptides with a broad spectrum. Recently human beta-defensin 2 (hBD-2) has been isolated from psoriatic skin; however, its exact localization and fate have not been fully understood. We studied the distribution pattern of hBD-2 in skin tissues of psoriasis and other inflammatory skin diseases. In the upper spinous and granular layer of psoriasis vulgaris hBD-2 was present in the cytoplasm. In the horny layer the positive signals were in a basket-weave pattern, indicating possible accumulation of hBD-2 in the intercellular space. The similar pattern of hBD-2 distribution was observed in the lesions of nummular eczema and atopic dermatitis. hBD-2 was not detected in the section of normal elbow and knee skin. When isolated psoriatic scales were stained, hBD-2 was detected in a wrapping paper-like distribution pattern surrounding the corneocytes. In horny layer of psoriatic skin hBD-2 was closely associated or colocalized with elafin, which is known to be in extracellular space, as demonstrated by double staining. Western blot analysis using cultured human keratinocytes detected hBD-2 with an expected size in the conditioned medium and in the cell lysates when stimulated with 5% FCS or IL-alpha. These results indicate that hBD-2 was synthesized and remained in cytoplasm in the upper spinous and granular layer, and then secreted into intercellular space in the horny layer. This dynamic change in hBD-2 distribution in epidermis is certainly relevant to function as an innate host defense mechanism against invading micro-organisms.

Differential expression and in vivo secretion of the antimicrobial peptides psoriasin (S100A7), RNase 7, human beta‐defensin‐2 and ‐3 in healthy human skin

“…As inducible AMP hBD-2 and -3 can be upregulated through different stimuli, this may be the reason why our analysis in healthy skin revealed rather low levels, a finding which is supported by previous reports (21)(22)(23).…”

Psychological stress downregulates epidermal antimicrobial peptide expression and increases severity of cutaneous infections in mice

“…Our immunoelectron-microscopic results support this scheme, because exogenous lipids clearly enhanced deposition of mBD3, but not CRAMP, within LBs in the face of ongoing PS. Not only endogenous lipids (64), but also both hBD2 and the hCAP product LL-37, are copackaged within epidermal LBs (37,38) and then cosecreted into the SC interstices (65). Our present results show that their murine homologs mBD3 and CRAMP were also assembled within epidermal LBs.…”

Differential mRNA Expression of Antimicrobial Peptides and Proteins in Atopic Dermatitis as Compared to Psoriasis Vulgaris and Healthy Skin

“…From the statistical point of view, the validity of previous data on AMP expression in AD and PV is limited because most studies included less than 15 patients per group [8, 9,17,18,19,20]. We therefore aimed to investigate AMPs expression in a larger population.…”