In Three Types of Interface Dermatitis, Different Patterns of Expression of Intercellular Adhesion Molecule-1 (ICAM-1) Indicate Different Triggers of Disease.

Abstract

We found distinct patterns of intercellular adhesion molecule-1 (ICAM-1) expression in three diseases characterized by interface dermatitis with mononuclear infiltrates and keratinocyte cytotoxicity: lichen planus (LP), subacute cutaneous lupus erythematosus (SCLE), and erythema multiforme (EM). In LP, basal keratinocytes show strong ICAM-1 expression associated with a dermal infiltrate, but ICAM-1 expression in the rest of the epidermis is minimal. In SCLE, there is diffuse epidermal ICAM-1 expression, sometimes with accentuation on the cell surface of basal cells. In EM, there is strong basal cell expression of ICAM-1 with evident cell surface accentuation, and also pockets of suprabasal expression with cell surface accentuation. These patterns are associated with different factors that trigger cytokine release in different locations. Both tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) produce greater relative ICAM-1 expression in basal keratinocytes than in more differentiated keratinocytes. In LP, the pure basal keratinocyte expression of ICAM-1 appears to be caused by cytokines, predominantly IFN-gamma, released by dermal lymphocytes. The pattern of ICAM-1 in SCLE corresponds to the pattern induced by ultraviolet radiation (UVR): diffuse epidermal ICAM-1 expression, sometimes with basal accentuation. Some individuals are "responders" to TNF-alpha or UVR, showing high levels of ICAM-1 expression following UVR or TNF-alpha stimulation in vitro or UVR stimulation in vivo. We propose that the pattern of ICAM-1 induction in SCLE is dependent on UVR-induced TNF-alpha release. EM is associated with apparent latent Herpes simplex virus, and Herpes simplex virus (HSV)-infected keratinocytes show enhanced ICAM-1 expression. We propose that in EM suprabasal ICAM-1 expression may be induced directly by HSV infection or indirectly through TNF-alpha release induced by HSV reactivation. Induction of ICAM-1 within the epidermis is stratified and individually variable. Basal keratinocytes show maximal induction of ICAM-1 expression due to innate sensitivity to TNF and IFN-gamma stimulation, and to location adjacent to dermal sources of cytokines. Suprabasal ICAM-1 can be induced by UVR and epidermal TNF-alpha release, and by factors such as viral infection. Different triggers of cytokine release and adhesion molecule induction may influence the different patterns of inflammation seen in diverse inflammatory skin diseases.

Interferon-γ Induces p11 Gene and Protein Expression in Human Epithelial Cells through Interferon-γ-activated Sequences in the p11Promoter

“…IFN-␥ has been reported to induce intercellular adhesion molecule-1 (ICAM-1) expression and vascular cell adhesion molecule-1 (VCAM) expression at the transcriptional and post-transcriptional level (17,18,34). Matsuura et al (16) reported that IFN-␥ induces COX-2 mRNA expression at the transcriptional level and increases PGE 2 synthesis in normal human epithelial keratinocytes cells.…”

“…IFN-␥ has been reported to regulate cyclooxygenase-2 (COX-2) expression and induce prostaglandin formation, which may play a major role in the induction of inflammatory processes (16). IFN-␥ also induces intercellular adhesion molecule-1 (ICAM-1), which plays an important role in the adherence and migration of leukocytes at sites of inflammation in several cell types (17,18). The binding of IFN-␥ to its surface receptor activates the receptor-associated tyrosine kinases, JAK1 and JAK2.…”

Differential Effects of Lipoprotein Lipase on Tumor Necrosis Factor-α and Interferon-γ-mediated Gene Expression in Human Endothelial Cells

“…Within target tissues, IFN-␥ induces expression of multiple chemokines, further enhancing leukocyte recruitment. IFN-␥ also induces the intercellular adhesion molecule (ICAM-1), which plays an important role in the adherence and migration of leukocytes at sites of inflammation (20,21). The binding of IFN-␥ to its surface receptor activates the receptor-associated tyrosine kinases, JAK1 and JAK2.…”

IFN-γ transgenic mice: clues to the pathogenesis of systemic lupus erythematosus?

“…Cutaneous lupus erythematosus (CLE) shares many features with IFN-γ induced skin disease: a dermal mono-nuclear infiltrate with FasL-positive immunocytes present [18], keratinocyte ICAM, MHC and Fas expression [19,20], abundant epidermal apoptotic cells (`sunburn cells') and loss of DCs from the epidermis [21,22]. Interestingly, CLE is a prominent feature of iatrogenic IFN-γ induced lupus in man [6].…”