ABSTRACT
IL-1beta, a major mediator of inflammatory and immunologic skin disease, undergoes post-translational site-specific cleavage by a novel cysteine protease termed IL-1beta-converting enzyme (ICE). Although in human skin keratinocytes produce significant amounts of the 31-kDa IL-1beta precursor protein, they fail under nonpathologic conditions to convert it to the 17.5-kDa bioactive form. In this study, we examined whether haptens and inflammatory agents might serve as stimuli for ICE activity in human keratinocytes, and, if so, whether ICE activity might precipitate enzymatic processing of IL-1beta to its 17.5-kDa form. Baseline levels of ICE mRNA were detected in keratinocyte cultures devoid of Langerhans cells and were up-regulated by nontoxic concentrations of the reactive hapten urushiol and by the irritant chemicals sodium lauryl sulfate and PMA. Although untreated keratinocytes expressed the 31-kDa form of the protein, 17.5-kDa IL-1beta was easily detected in keratinocytes and keratinocyte supernatants treated with either urushiol or the irritant chemicals. Enzymatic conversion from the 31-kDa to the 17.5-kDa form of IL-1beta was blocked by addition of a highly specific aldehyde inhibitor that contained a tetrapeptide recognition sequence specific for ICE, but not by an aldehyde inhibitor of a related ICE-like cysteine protease. Induction of IL-1beta-converting enzyme by immunologic and inflammatory stimuli may be one of the key regulatory elements in the pathogenesis of allergic and irritant contact hypersensitivity.
Subject(s)
Cysteine Endopeptidases/biosynthesis , Interleukin-1/biosynthesis , Keratinocytes/enzymology , Keratinocytes/immunology , Caspase 1 , Catechols/pharmacology , Cells, Cultured , Cysteine Endopeptidases/genetics , Cysteine Proteinase Inhibitors/pharmacology , Enzyme Activation/drug effects , Enzyme Induction/genetics , Enzyme Induction/immunology , Extracellular Space/metabolism , Humans , Inflammation/enzymology , Inflammation/immunology , Interleukin-1/antagonists & inhibitors , Interleukin-1/metabolism , Keratinocytes/metabolism , Keratinocytes/pathology , Molecular Weight , Oligopeptides/pharmacology , Protein Kinase C/antagonists & inhibitors , Protein Kinase C/metabolism , RNA, Messenger/biosynthesisABSTRACT
Interleukin 6 (IL-6) is an endogenous cytokine with multiple biological functions, including amplification of the inflammatory response. Recombinant human IL-6, administered as part of a chemotherapeutic regimen, has recently been shown to cause regression of certain types of malignant tumours. We report a patient who developed a cutaneous eruption consisting of coalescent, erythematous, scaling macules and papules after administration of recombinant human IL-6, given as part of her chemotherapy for ductal carcinoma of the breast.
Subject(s)
Drug Eruptions/etiology , Interleukin-6/adverse effects , Adult , Drug Eruptions/pathology , Female , Humans , Recombinant Proteins/adverse effects , Skin/pathologyABSTRACT
A case of malignant fibrous histiocytoma resembling mycetoma is reported. We describe a patient with a draining purulent mass and localized swelling of the left ankle. The lesion's ulcerated surface produced purulent material that contained black "granules" resembling those seen in mycetoma. Cultures revealed a heavy growth of Staphylococcus aureus and no growth of fungi. Treatment with oral antibiotics resulted in resolution of the infection with persistence of the mass. Histopathologic examination of the mass was consistent with malignant fibrous histiocytoma. This case represents an example of a malignant lesion whose initial presentation was complicated by a bacterial infection resembling a mycetoma.
Subject(s)
Enterobacter , Histiocytoma, Benign Fibrous/diagnosis , Mycetoma/diagnosis , Skin Neoplasms/diagnosis , Staphylococcus aureus , Adult , Ankle , Diagnosis, Differential , Female , Humans , Mycetoma/microbiologyABSTRACT
Photon counting is used in this instrument to obtain high precision in the measurement of the intensity, degree of polarization, and orientation of the plane of polarization of light in the natural environment. The dual-channel configuration, with four interference filters in each channel, provides the possibility of measurements in eight narrow spectral intervals in the wavelength range 0.32-0.90 microm. Operation of the device, including rotation of the polarizing prism, selection of the filters, orientation in azimuth and elevation, and other mechanical processes, is controlled completely by a small electronic computer. The measurements are reduced to the physical quantities of interest on a real-time basis by the computer, which also is used to record the data on magnetic tape and print them out on a high speed printer as desired. Field operation has shown the instrument to be fast and reliable for measuring the intensity and polarization of sunlight, which may be of interest for characterizing atmospheric processes or the physical properties of natural surfaces.
