Dynamic alteration of human beta-defensin 2 localization from cytoplasm to intercellular space in psoriatic skin.
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.
Huh
Wook-Kang
WK
Department of Dermatology, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. wookkang@cc.okayama-u.ac.jp
Oono
Takashi
T
Shirafuji
Yoshinori
Y
Akiyama
Hisanori
H
Arata
Jirô
J
Sakaguchi
Masakiyo
M
Huh
Nam-Ho
NH
Iwatsuki
Keiji
K
D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology; D015153:Blotting, Western; D003593:Cytoplasm / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011565:Psoriasis / Q000276:immunology / Q000378:metabolism*; D023083:beta-Defensins / Q000378:metabolism*
D000890:Anti-Infective Agents; C106641:DEFB4A protein, human; D007375:Interleukin-1; D023083:beta-Defensins