Here, we investigated whether an anti-allergy drug, terfenadine, affects interleukin-4-modulated cytokine expression in peripheral T cells. Peripheral blood T cells were first stimulated with recombinant interleukin-4 and then tested for modulation of the mRNA of a panel of cytokines using the reverse transcription-polymerase chain reaction followed by Southern blot analysis. It was found that T cells constitutively expressed mRNA specific to T helper 1 cytokines (interleukin-2, interferon-gamma, tumor necrosis factor-alpha), which was markedly downregulated upon stimulation with interleukin-4, whereas mRNA for T helper 2 cytokines such as interleukins 4, 5, and 6 was induced in response to interleukin-4. Interestingly, the interleukin-4-induced expression of all T helper 2 cytokines examined was markedly downregulated by terfenadine. Among T helper 1 cytokines, interleukin-4-mediated suppression of tumor necrosis factor-alpha was not affected by terfenadine, which, however, markedly restored mRNA expression of interferon-gamma or interleukin-2. Electrophoretic mobility shift assays using [32P]-labeled synthetic oligonucleotides encoding the consensus binding motif of activator protein-1 demonstrated that interleukin-4-induced binding of activator protein-1 composed of JunB was interfered by terfenadine. This study indicates that terfenadine, at least partially, interferes with interleukin-4-activated signaling, leading to terfenadine antagonism against the modulatory impact of interleukin-4 on T cell cytokines.

PURPOSE:To investigate the effects of epinastine on eosinophil chemotaxis and changes in eosinophil adhesion molecules induced by epinastine and three other antiallergic agents, using eosinophils of atopic dermatitis (AD) patients.RESULTS:Epinastine reduced eosinophil chemotaxis toward eotaxin when the eosinophils had been prestimulated with interleukin (IL)-5, but given alone it did not alter eosinophil chemotaxis toward IL-5. CD11b expression was inhibited when peripheral blood was prestimulated with IL-5, but eosinophil adhesion molecule expression was not altered.CONCLUSIONS:Epinastine suppresses allergic inflammation not only through its strong antihistamine and antimediator effects, but also by inhibiting eosinophilic chemotaxis and the expression of adhesion molecules involved in chemotaxis, especially CD11b.

Background Despite the increasing incidence of basal cell carcinoma (BCC), its pathogenesis has remained largely unknown. Recently, it was reported that genes involved in tissue morphogenesis, such as sonic hedgehog or patched, were found to be mutated in BCC, suggesting the involvement of those molecules in the pathogenesis of this tumour. Furthermore, there is evidence that the Wnt-mediated signalling pathway may be one of the downstream targets of sonic hedgehog-mediated signalling, which has led us to focus on molecular events on the Writ pathway in BCC. Among the signal transducers involved in the Wnt pathway, it is clear that beta -catenin plays a pivotal role in the promotion of morphogenesis and cell growth. In respect to this, it has been reported that, in particular circumstances, as in colorectal cancers, beta -catenin migrates to the nuclei, where it exerts an ability to activate the transcription of various genes.Objectives To investigate the cellular distribution of beta -catenin in skin tumours, in particular, in BCC.Methods Twenty skin biopsy specimens derived from BCC, 10 from inflammatory skin diseases and five from squamous cell carcinomas were immunostained with an antibody directed against beta -catenin.Results Fourteen of the 20 BCC samples tested showed nuclear localization of beta -catenin, while none of the other samples gave rise to positive nuclear staining.Conclusions Nuclear localization of beta -catenin is a characteristic feature of BCC; this suggests its tumorigenic role in this tumour. This gives us a further insight into the molecular pathogenesis of BCC.

Sebaceous nevus is wellknown for secondary tumor formation after puberty, e.g. syringocytadenoma papilliferum, apocrine cystadenoma, hidradenoma, trichilemmoma, osteoma, and basal cell carcinoma. Sebaceous nevus syndrome is a rare disorder characterized by sebaceous nevus and central nervous system abnormalities. However, skin tumors occurring in sebaceous nevus syndrome have not been reported. We describe a patient with sebaceous nevus syndrome who developed basal cell carcinoma on her lesion of sebaceous nevus.