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Interleukin-18 (IL-18) is an 18-kDa cytokine produced by lipopolysaccharide (LPS)-activated macrophages or Kupffer cells. In addition, IL-18 is also produced by many different types of cells and tissues, including epidermal keratinocytes, the adrenal cortex, and the brain. IL-18 acts on the immune system to increase IFN-gamma production from T and NK cells to enhance NK cell cytotoxicity and to activate Th1 cell proliferation. It is considered that the tissue expression of cytokines and cell adhesion molecules such as ICAM-1 are common in graft-versus-host disease (GVHD). Recent evidence suggests that IL-18 is a cytokine relevant in the pathogenesis of GVHD. Despite the potential importance of IL-18 in GVHD, the distribution of IL-18 production in cutaneous GVHD has not been fully investigated. In this study, the expression of IL-18 in the cutaneous GVHD was investigated. Formalin-fixed, paraffin-embedded tissue sections were obtained, and immunohistochemical analysis was performed to detect IL-18 and ICAM-1 expression according to the acute and chronic GVHD. Immunohistochemical analysis confirmed the enhanced IL-18 expression levels in the early stage (grade 1) of acute GVHD and the late stage (sclerodermoid) of chronic GVHD compared to the other stages. In contrast, the ICAM-1 expression level was constant at all stages. Our findings indicate that IL-18 is a significant pathogenic indicator in cutaneous GVHD, and the tissue expression of IL-18 seems to be associated with the pathogenesis of acute and chronic GVHD.

NGFI-B is an immediate-early gene that encodes an orphan nuclear receptor. In the rat ovary, the preovulatory surge of LH induces NGFI-B expression in granulosa cells of preovulatory follicles, reaching a peak within 1 h and declining to control levels at 6 h. The LH-stimulated NGFI-B expression is abolished by alpha-amanitin, but superinduced by cycloheximide. Similarly, treatment of human luteinized granulosa cells with LH causes a rapid and transient stimulation of NGFI-B expression. Interestingly, the induction of NGFI-B expression in response to LH stimulation in preovulatory granulosa cells requires signaling through protein kinase Czeta. Furthermore, two other NGFI-B family members, Nurr1 and Nor1, are also rapidly stimulated by LH in granulosa cells of preovulatory follicles through the activation of protein kinase Czeta. The cell-type specific expression and LH induction of NGFI-B suggests a potential role of NGFI-B in the ovulatory process.

Mutations of p53 and PTCH gene, two candidate tumor suppressor genes for basal cell carcinoma (BCC), were screened in 15 cases of sporadic BCCs that developed in sun-exposed skin region in a Korean population. p53 and PTCH mutations were detected at a frequency of 33 and 40%, respectively, and the mutations were predominantly UV-signature transition, C-->T transitions at dipyrimidine sites and CC-->TT tandem mutations. In both genes, the most common mutations were missense mutations resulting in amino acid substitution, which is different than the results from Caucasian BCCs where mutations are frequently predicted to make truncated or absent proteins. All mutations, except for one, occurred on the nontranscribed strand where is little efficient removal of UV-induced pyrimidine dimers relative to the transcribed strand. Loss of heterozygocity (LOH) of 9q22 for PTCH loci was found in eight of 15 informative cases of BCCs (53%), but none of the cases were informative for LOH of 17p13 for p53 loci. Not only do our data indicate the key role played by p53 and PTCH in the development of BCCs, these findings also suggest that UVB may significantly contribute to BCC tumorigenesis. Moreover, molecular epidemiology composed of incidence of p53 and PTCH mutations, difference in the type of mutation and repair bias of UV-induced DNA lesions might affect the distinct features of BCCs between different racial population.