Transforming growth factor‐β1 localization in normal and psoriatic epidermal keratinocytes in situ

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Abstract
Transforming growth factor‐β1 (TGFβ1) is a potent inhibitor of epithelial cell proliferation and its effects on growth and differentiation have been extensively characterized in cultured keratinocytes. We used two TGFβ1‐specific polyclonal antibodies (anti‐LC and anti‐CC) to determine the presence of TGFβ1 peptide in keratinocytes in sections of normal human skin in situ and in both plaque and nonplaque skin from individuals with psoriasis. In contrast to the differentiation phenotype expressed by keratinocytes in normal epidermis, keratinocytes in the psoriatic plaque exhibit a hyperproliferative/regenerative differentiation phenotype. Anti‐TGFβ1 staining was observed primarily in the epidermis. Anti‐LC TGFβ1 antibody stained nonproliferating, differentiated suprabasal keratinocytes intracellularly in normal skin but did not stain psoriatic plaques from five of seven patients. In contrast, anti‐CC TGFβ1 antibody stained suprabasal keratinocytes extracellularly in psoriatic plaques, but did not stain normal skin. Both anti‐LC and anti‐CC stained suprabasal keratinocytes intracellularly in nonplaque psoriatic skin. Thus, the conformation or structure of TGFβ1 and its localization vary in keratinocytes with distinct differentiation phenotypes suggesting that TGFβ1 is a potential modulator of keratinocyte differentiation in vivo. Selective association of TGFβ1 with nonproliferating keratinocytes in the suprabasal layers of the epidermis and its exclusion from the proliferating keratinocytes in the basal layer suggest that it may be a Physiological regulator of keratinocyte proliferation. In addition, the intracellular localization of TGFβ1 peptide in both normal and psoriatic keratinocytes suggests that it is constitutively synthesized by epidermal keratinocytes in vivo.