Expression of keratins 8, 18, and 19 in epithelia of atrophic oral lichen planus

Abstract

Keratins form intermediate filaments of the cytoskeleton in keratinocytes and have roles in cell structure, signaling, intracellular transport, and cell death. Oral lichen planus (OLP) is an oral inflammatory disease with derangements in basal keratinocytes and disruption of the basal membrane. Here, we focused on epithelial expression of keratins 8, 18, and 19 because these proteins are known to modulate cell death. Biopsies were taken from buccal oral mucosa of persons with normal oral mucosa (n = 10) or atrophic OLP (n = 10). Cultured normal oral keratinocytes (n = 4) showed expression of mRNA and protein for keratins 8, 18, and 19. Immunohistochemistry showed consistent staining for keratins 8 and 18 in basal keratinocytes of normal oral mucosa. In OLP, staining for keratin (K)8 was mostly negative and staining for K18 was weak. Keratin 19 was expressed irregularly in most biopsies of normal oral mucosa and not at all in OLP. Several mononuclear leukocytes in the cellular infiltrate showed membrane staining for K8 and K18. Positive staining for K16 confirmed partial collapse of the basal cell layer in OLP. The basal cell niche in OLP therefore appeared to be partly populated with keratinocytes demonstrating a higher degree of differentiation (K8− K18− K19− K16+); consequently, such areas may be more susceptible to the action of cell death factors released from the cell infiltrate as a result of lacking the protective, normal keratin present in the basal epithelial cell layer of normal oral mucosa.

Composition of hemidesmosomes in basal keratinocytes of normal buccal mucosa and oral lichen planus

“…The increased staining of plectin pS4642 along the basal membrane in OLP may therefore point towards a disabled binding of keratins. This coincides with the failing expression of K18 that we previously observed (10), since K18 is able to bind to plectin only (11). Release of plectin from keratin also initiates the release of plectin from integrin‐ β 4.…”

“…This can be induced by growth factors, tumor necrosis factor, or calcium signaling (reviewed in 7). Another explanation for a possible increase in phosphorylation of integrin β 4 can be loss of K8/18 expression in basal keratinocytes in OLP epithelium (10), as keratins can prohibit phosphorylation by acting as a phosphate ‘sponge’ (41). The reduced expression of K8/18 and K5 in basal keratinocytes in OLP epithelium (10,42) can also explain the cytoplasmic localization of integrin‐ α 6 β 4 in ATR‐OLP because keratins stabilize hemidesmosomes through regulation of integrin‐ β 4 turnover and keep integrin‐ α 6 β 4 localized to the cell membrane (40).…”

“…Another explanation for a possible increase in phosphorylation of integrin β 4 can be loss of K8/18 expression in basal keratinocytes in OLP epithelium (10), as keratins can prohibit phosphorylation by acting as a phosphate ‘sponge’ (41). The reduced expression of K8/18 and K5 in basal keratinocytes in OLP epithelium (10,42) can also explain the cytoplasmic localization of integrin‐ α 6 β 4 in ATR‐OLP because keratins stabilize hemidesmosomes through regulation of integrin‐ β 4 turnover and keep integrin‐ α 6 β 4 localized to the cell membrane (40). In RET‐OLP, the more quiescent form of OLP, K8/18 expression is less affected (O. Schreurs, A. Karatsaidis, K. Schenck, unpublished data), and this might keep integrin‐ α 6 β 4 membrane‐located as presently observed.…”

“…The keratins form filaments that extend from the nucleus to hemidesmosomes and desmosomes in the internal leaflet of the plasma membrane. Under healthy conditions, basal keratinocytes of oral, non‐keratinizing stratified epithelia express the keratin dimers K5/K14 and K5/K15 that can bind to dystonin and plectin 1a, and K8/K18 and K8/K19 that can bind to plectin (8–12).…”

“…Immunostaining for laminin‐332, laminin‐111, and collagen type IV in OLP has been described as a absent, discontinuous, intensified, or thickened bands with finger‐like projections into the connective tissue, while it was seen as a continuous band along the basement membrane in normal oral mucosa (18–20). Intracellularly, K8, K18, and K19 are absent or strongly reduced in OLP, as compared with normal oral mucosa (10).…”