Keratinocytes produce not only interleukin 1 (IL-1) but also IL-1 receptor antagonist (IL-1ra), a competitive inhibitor of IL-1. Because little is known about the presence of IL-1ra in the stratum corneum, we examined the content of IL-1ra in the stratum corneum, especially the balance between IL-1 and IL-1ra. IL-1 alpha and IL-1ra, but not IL-1 beta, were detected in the tape-stripped stratum corneum of healthy volunteers by enzyme-linked immunosorbent assays. IL-1 alpha and IL-1ra were bioactive as determined by thymocyte co-stimulation assay, and their molecular masses were 17 and 20 kDa, respectively, suggesting that the stratum corneum contains active forms of IL-1 alpha and IL-1ra produced by keratinocytes. The stratum corneum of an unexposed area, the inner side of the upper arm. contained more IL-1 alpha than a sun-exposed area, the face. In contrast, the stratum corneum of the sun-exposed area contained a markedly higher amount of IL-1ra than that of the unexposed area. The ratio of IL-1ra to IL-1 alpha was 8 in the unexposed area, and over 100 in the sun-exposed area. Therefore, IL-1 alpha activity was dominant in the unexposed area, and in contrast, IL-1ra activity was dominant in the sun-exposed area. An elevated level of IL-1ra was detected in the stratum corneum of the sun-exposed area independently of age. In the unexposed area, however, IL-1a increased, but IL-1ra decreased, with age, resulting in a significant decline of the ratio of IL-1ra to IL-1a with increasing age. Irradiation of 2 MED of ultraviolet B to the back skin, an unexposed area, resulted in striking elevation of IL-1ra in the stratum corneum in desquamating scales. These data suggest that IL-1ra in the epidermis may be inducible by chronic UV irradiation, although IL-1ra production in the epidermis may decrease with aging in the absence of any stimulus. IL-1ra in the epidermis may play a role in the regulation of IL-1-induced inflammatory responses, and an appropriate balance between IL-1 and IL-1ra may help to maintain homeostasis of the skin.

IL-1 receptor antagonist (IL-1ra) is a cytokine that competitively binds the IL-1 receptor to antagonize IL-1 activity without any agonist function. Previous experiments indicated that the ratio of IL-1ra to IL-1alpha in the normal stratum corneum (SC) was much higher in the sun-exposed face than in the sun-protected area, upper arms. It was also reported by another laboratory that IL-1ra is increased in the lesional skin of psoriatic patients. This study was designed to measure the contents of IL-1alpha and IL-1ra in non-lesional and pathological SC obtained from inflammatory skin diseases including psoriasis and non-psoriatic dermatoses such as atopic dermatitis. The SC materials were obtained with a non-invasive tape-stripping method. Their soluble fractions were prepared and assayed for IL-1alpha and IL-1ra by enzyme-linked immunosorbent assays. As a result we confirmed the previous findings that the ratio of IL-1ra to IL-1alpha in the normal SC was much higher in the face than in the sun-protected sites, the trunk as well as extremities. Next, we found that IL-1alpha contents were significantly reduced in the SC samples obtained from inflammatory skin regardless of whether their IL-1ra contents increased or unchanged. Moreover, we noted that an increased ratio of IL-1ra to IL-1alpha in the SC was not specific to psoriasis, but was also found in other inflammatory skin diseases including atopic dermatitis. This ratio was found to become lower after successful treatment of these skin lesions with topical glucocorticoids. We conclude from these observations that the increased ratio of IL-1ra to IL-1alpha in the SC is a non-specific phenomenon that can occur in any inflammatory skin diseases regardless of the inflammatory pattern, probably reflecting a skin regulation process against various kinds of inflammation.

Cortactin and the translocated intimin receptor, Tir, interacted with each other in pedestal formation in HeLa cells infected with enteropathogenic Escherichia coli (EPEC). Cortactin is shown to be necessary for organizing actin pedestals in response to EPEC, based on the expression of green fluorescent protein-fused cortactin derivatives in HeLa cells.

No abstract

SummaryEnteropathogenic Escherichia coli (EPEC) is able to inject its own receptor, a transmembrane protein called translocated intimin receptor, Tir, into the host epithelial cell. The bacterium then uses an outer membrane protein, intimin, to bind to Tir and remains firmly attached to the host cell surface for the duration of the infection. The bacterium is also able to trigger the rearrangement of several host cell proteins, culminating with the formation of an actinrich, pedestal-like structure beneath the EPEC adherence site. Although several cytoskeletal proteins are rearranged following EPEC infection, the exact role played by these proteins during pedestal formation remains unknown. We report here that talin, an integrin-binding protein, is recruited by EPEC and associates directly with Tir. By surface plasmon resonance (SPR), the predicted value for the dissociation constant (K D ) for Tir±talin binding was 1.86 Â 10 27 M. We also demonstrate that microinjection of anti-talin antibodies into HeLa cells resulted in the complete inability to focus actin filaments beneath the attached bacterium. These findings demonstrate that talin is essential for EPEC-induced pedestal formation in infected cells.

The present study demonstrated that we can measure both urea forms in the skin after the application of urea-containing creams. The proposed technique would be useful in the evaluation of characteristics of the penetration behavior of urea in the skin after the application of various urea-containing moisturizers.

The Stipsicz conjecture on the fiber-sum decomposability of Lefschetz fibrations states that nonminimal Lefschetz fibrations over S 2 are irreducible with respect to fiber-sum decompositions. We can conclude that such Lefschetz fibrations are prime and fundamental. In this paper, we determine the canonical classes of nonminimal Lefschetz fibrations admitting spheres of square −1 whose total intersection number with generic fiber is big. As a consequence, we consider the Kodaira dimension and the geography problem of such Lefschetz fibrations.

A modified guinea pig testing technique was developed for the detection of weak allergens and allergenicity of materials unsuitable for testing by intradermal injection. This test involved the use of Freund's complete adjuvant to stimulate the immune system of the animal, and external application instead of intradermal injection of the test compound in the induction stage. The allergenicity of Sudan III, Brilliant Lake Red R and Sudan I was tested by this procedure. In the dose-effect study of Sudan I, the dose dependency of a positive reaction of the induction and challenge concentrations was recognized. The test was compared with three other guinea pig sensitization tests. The results obtained with this test correlated well with those obtained with the guinea pig maximization test.