Immunocytochemical Localization of Lysosomal Cysteine and Aspartic Proteinases, and Ubiquitin in Rat Epidermis.

Sato, Ken; Waguri, Satoshi; Ohsawa, Yoshiyuki; Nitatori, Tohru; Kon, Saiichi; Kominami, Eiki; Watanabe, Tsuyoshi; Gotow, Takahiro; Uchiyama, Yasuo

doi:10.1679/aohc.60.275

Cited by 14 publications

(19 citation statements)

References 33 publications

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“…Until present most analyses of cathepsin expression have been performed in dermal cell culture and only two studies show expression of cathepsins B, C, D, H, L in human and rat epidermis (38,39). Our study revealed that unlike the latter cathepsins, CATS is not expressed in normal keratinocytes.…”

Section: Discussionmentioning

confidence: 55%

Upregulation of cathepsin S in psoriatic keratinocytes

Schönefuß

Wendt

Schattling

et al. 2010

Experimental Dermatology

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Cathepsin S (CATS) is a cysteine protease, well known for its role in MHC class II-mediated antigen presentation and extracellular matrix degradation. Disturbance of the expression or metabolism of this protease is a concomitant feature of several diseases. Given this importance we studied the localization and regulation of CATS expression in normal and pathological human ⁄ mouse skin. In normal human skin CATSimmunostaining is mainly present in the dermis and is localized in macrophages, Langerhans, T-and endothelial cells, but absent in keratinocytes. In all analyzed pathological skin biopsies, i.e. atopic dermatitis, actinic keratosis and psoriasis, CATS staining is strongly increased in the dermis. But only in psoriasis, CATSimmunostaining is also detectable in keratinocytes. We show that cocultivation with T-cells as well as treatment with cytokines can trigger expression and secretion of CATS, which is involved in MHC II processing in keratinocytes. Our data provide first evidence that CATS expression (i) is selectively induced in psoriatic keratinocytes, (ii) is triggered by T-cells and (iii) might be involved in keratinocytic MHC class II expression, the processing of the MHC class II-associated invariant chain and remodeling of the extracellular matrix. This paper expands our knowledge on the important role of keratinocytes in dermatological disease.

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Section: Discussionmentioning

confidence: 55%

Upregulation of cathepsin S in psoriatic keratinocytes

Schönefuß

Wendt

Schattling

et al. 2010

Experimental Dermatology

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“…However, the cytoplasm of those cells showed no UB-positive reaction. Besides ALS, it was reported that UB was expressed in the nuclei of the epidermal cells [37,38]. The accumulation of ubiquitinated proteins may be the most likely cause of increased UB immunoreactivity [39].…”

Section: Discussionmentioning

confidence: 99%

An immunohistochemical study of ubiquitin in the skin of sporadic amyotrophic lateral sclerosis

Watanabe

Okeda

Yamano

et al. 2010

Journal of the Neurological Sciences

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“…Paraffin-embedded sections were immunostained by a method described elsewhere (16). Sections were treated with anti-Bcl-2 Ab …”

Section: Methodsmentioning

confidence: 99%

Accelerated apoptosis of lymphocytes by augmented induction of Bax in SSI-1 (STAT-induced STAT inhibitor-1) deficient mice

Naka

Matsumoto

Narazaki

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

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269

194

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Growth, differentiation, and programmed cell death (apoptosis) are mainly controlled by cytokines. The Janus kinase-signal transducers and activators of transcription (JAK-STAT) signal pathway is an important component of cytokine signaling. We have previously shown that STAT3 induces a molecule designated as SSI-1, which inhibits STAT3 functions. To clarify the physiological roles of SSI-1 in vivo, we generated, here, mice lacking SSI-1. These SSI-1؊͞؊ mice displayed growth retardation and died within 3 weeks after birth. Lymphocytes in the thymus and spleen of the SSI-1؊͞؊ mice exhibited accelerated apoptosis with aging, and their number was 20-25% of that in SSI-1؉͞؉ mice at 10 days of age. However, the differentiation of lymphocytes lacking SSI-1 appeared to be normal. Among various pro-and anti-apoptotic molecules examined, an up-regulation of Bax was found in lymphocytes of the spleen and thymus of SSI-1؊͞؊ mice. These findings suggest that SSI-1 prevents apoptosis by inhibiting the expression of Bax.The homeostatic regulation of cell populations is controlled by a balance among proliferation, growth arrest, and apoptosis, and this balance is mainly controlled by cytokines and growth factors. Cytokines act by binding to receptors expressed on the surfaces of responsive cells, which are associated with one or more members of the Janus kinase (JAK) family of cytoplasmic tyrosine kinases. The JAK-signal transducers and activators of transcription (STAT) signal pathway plays an important role in cytokine signaling (1-3), and is unique in that it features a direct linkage of receptor-ligand interaction on the cell surface to gene expression in the nucleus (4-6). However, the mechanism of negative control of cytokine actions involved in limiting their signal transductions is comparatively less well characterized. In 1997, the molecules that were expressed by stimulation of cytokine such as interleukin 6 (IL-6) and inhibited cytokine signal transmission by binding to JAK were isolated [STAT-induced STAT inhibitor-1 (SSI-1), suppressor of cytokine signaling (SOCS-1), Jak-binding protein (JAB)] (7-9). Subsequently, SSI-1 was found to form a family consisting of at least eight molecules, which were structurally characterized by an SH2 domain and a C-terminal conserved region (SC-motif͞SOCS-box͞CH-domain) (10-12), and it was recently known that SSI-1 inhibits not only IL-6 signaling but also interferon (IFN)-␥, IL-2, IL-3, and growth hormone signaling in vitro (13). It is expected that further study of SSI family molecules engaged in the negative feedback mechanism of cytokines will clarify the control mechanism of cytokines, which have remained obscure. MATERIALS AND METHODS Generation of SSI-1-Deficient Mice.A 129͞G mouse genomic library (Stratagene) containing the SSI-1 gene was screened, subcloned into the pBluescript vector, and characterized by restriction endonuclease mapping and DNA sequencing. A targeting vector was designed to replace the SSI-1 intron with phosphoglycerate kinase neo. This targeting...

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Immunocytochemical Localization of Lysosomal Cysteine and Aspartic Proteinases, and Ubiquitin in Rat Epidermis.

Cited by 14 publications

References 33 publications

Upregulation of cathepsin S in psoriatic keratinocytes

Upregulation of cathepsin S in psoriatic keratinocytes

An immunohistochemical study of ubiquitin in the skin of sporadic amyotrophic lateral sclerosis

Accelerated apoptosis of lymphocytes by augmented induction of Bax in SSI-1 (STAT-induced STAT inhibitor-1) deficient mice

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