bromochloroacetic-acid and Skin-Diseases--Viral

The palmoplantar epidermis is a specialized area of the skin that undergoes high levels of mechanical stress. The palmoplantar keratinization and esophageal cancer syndrome, tylosis with esophageal cancer, is linked to mutations in RHBDF2 encoding the proteolytically inactive rhomboid protein, iRhom2. Subsequently, iRhom2 was found to affect palmoplantar thickening to modulate the stress keratin response and to mediate context-dependent stress pathways by p63. iRhom2 is also a direct regulator of the sheddase, ADAM17, and the antiviral adaptor protein, stimulator of IFN genes. In this perspective, the pleiotropic functions of iRhom2 are discussed with respect to the skin, inflammation, and the antiviral response.

Topics: ADAM17 Protein; Animals; Carrier Proteins; Dermatitis; Disease Models, Animal; Epidermis; Esophageal Neoplasms; Foot; Gene Expression Regulation; Hand; Host Microbial Interactions; Humans; Intracellular Signaling Peptides and Proteins; Keratinocytes; Keratins; Keratoderma, Palmoplantar; Mice; Mice, Knockout; Mutation; Signal Transduction; Skin Diseases, Viral; Transcription Factors; Tumor Suppressor Proteins

Topics: Acne Vulgaris; Acyclovir; Adult; Aged; Antiviral Agents; Epithelium; Female; Follow-Up Studies; Hair Follicle; Herpes Zoster; Humans; Keratins; Lymphocytes; Male; Middle Aged; Skin Diseases, Viral

After interferon (IFN) treatment of patients with condyloma acuminatum, groups clinically proven to be responders or nonresponders were selected, and cellular parameters that might influence the clinical response were studied in pretreatment biopsies by reverse transcription polymerase chain reaction (RT-PCR). The nonresponders were found to express higher amounts of cellular proliferative markers, such as proliferating cell nuclear antigen (PCNA), cyclin A, and cdc 2 kinase, but lower levels of growth suppressor genes (TGF-beta 1, TGF-beta 2 and p53) before IFN treatment. The responders retained the epidermal keratinization, except for some signs of hyperproliferation (K6, K16 cytokeratins). In addition, the nonresponders showed a shift in the keratinization pattern to a mucosal or fetal type, as evidenced by high expression of the K18, K6, K16 and K13 cytokeratins but decreased K5, K14 and K10 levels before treatment. The expression of the human papillomavirus (HPV) genes is consistent with these differentiation patterns. The crucial conclusion to be drawn from this study is that those condylomas whose pretreatment phenotype most closely resembles that of normal epidermis respond to IFN treatment, whereas those more akin to nonkeratinizing epithelia fail to respond, i.e. the resistance of condylomas to IFN treatment is correlated with dedifferentiation.

Topics: Base Sequence; Biomarkers; Cell Differentiation; Condylomata Acuminata; DNA Primers; Gene Expression Regulation, Viral; Genes, Viral; Humans; Interferons; Keratins; Papillomaviridae; Polymerase Chain Reaction; RNA, Messenger; RNA, Viral; Skin Diseases, Viral