Localization of the human SH-protease inhibitor in the epidermis

Räsänen, O; Järvinen, Mikko; Rinne, Ari

doi:10.1016/s0065-1281(78)80025-7

Cited by 29 publications

(16 citation statements)

References 6 publications

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“…23 Recently, the crystal structure of stefin B tetramer has been determined which involves Pro at the position 74 in a cis isomeric state being essential in stefin B amyloid-fibril formation. 24,25 Stefin A was purified from rat skin as a first identified mammalian cystatin 26 and has been found in other epithelial cells, [27][28][29][30][31] in neutrophils from the liver, 32 in dendritic reticulum cells of lymphoid tissue, 33 in Hassall's corpuscles and in thymic medullary cells. 34 The selective expression of the inhibitor correlates with the tissues participating in the first-line defence against pathogens.…”

Section: Type I Cystatinsmentioning

confidence: 99%

Cystatins in Immune System

2013

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Cystatins comprise a large superfamily of related proteins with diverse biological activities. They were initially characterised as inhibitors of lysosomal cysteine proteases, however, in recent years some alternative functions for cystatins have been proposed. Cystatins possessing inhibitory function are members of three families, family I (stefins), family II (cystatins) and family III (kininogens). Stefin A is often linked to neoplastic changes in epithelium while another family I cystatin, stefin B is supposed to have a specific role in neuredegenerative diseases. Cystatin C, a typical type II cystatin, is expressed in a variety of human tissues and cells. On the other hand, expression of other type II cystatins is more specific. Cystatin F is an endo/lysosome targeted protease inhibitor, selectively expressed in immune cells, suggesting its role in processes related to immune response. Our recent work points on its role in regulation of dendritic cell maturation and in natural killer cells functional inactivation that may enhance tumor survival. Cystatin E/M expression is mainly restricted to the epithelia of the skin which emphasizes its prominent role in cutaneous biology. Here, we review the current knowledge on type I (stefins A and B) and type II cystatins (cystatins C, F and E/M) in pathologies, with particular emphasis on their suppressive vs. promotional function in the tumorigenesis and metastasis. We proposed that an imbalance between cathepsins and cystatins may attenuate immune cell functions and facilitate tumor cell invasion.

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Section: Type I Cystatinsmentioning

confidence: 99%

Cystatins in Immune System

2013

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“…Stefin A has a broad inhibitory profile, but shows selective expression in tissues involved in the first-line immune response like skin epithelial cells (46) and polymorphonuclear granulocytes (47); it might be thus relevant for inhibiting peptidases from microbes invading through the skin. Furthermore, stefin A was proposed to have an important function in the development of the epidermis and in the associated neonatal immune response (48).…”

Section: Cystatins and The Immune Responsementioning

confidence: 99%

Cystatins, cysteine peptidase inhibitors, as regulators of immune cell cytotoxicity

et al. 2017

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Cystatins comprise a superfamily of evolutionarily related proteins, present in all living organisms, from protozoa to mammals. They act as inhibitors of cysteine peptidases although they can also function independently of their inhibitory function. Cysteine cathepsins are implicated in various physiological and pathological processes. In the immune response they are involved in antigen processing and presentation, the cytotoxicity of natural killer (NK) cells and cytotoxic T lymphocytes (CTL), migration and adhesion of immune cells, cytokine and growth factor regulation and toll-like receptor signalling. Cystatins are probably involved in the regulation of all these processes; importantly, cystatin F has a crucial role in the regulation of immune cell cytotoxicity. NK cells and CTLs exploit the granzyme/perforinAmong those peptidases involved in immune processes, many studies have been focused on a group of endosomal/lysosomal cysteine peptidases, the cysteine cathepsins, whose involvement in antigen processing and presentation, cytotoxicity of natural killer (NK) cells and cytotoxic T lymphocytes (CTL), migration and adhesion of immune cells, cytokine and growth factor regulation and toll like receptor (TLR) signalling have been demonstrated (3,4). In addition to cathepsins, another lysosomal cysteine peptidase, legumain or asparaginyl endopeptidase, has also been associated with the immune response, most notably with antigen presentation and TLR signalling (4, 5). The activities of cysteine cathepsins and legumain are regulated on different levels. Their expression, for example, is regulated at transcriptional or translational levels. They are synthesised as inactive precursors, activated only at the site of action, and compartmentalised into lysosomes or other organelles. Their activity can be regulated by oxidation of the active site cysteine or by endogenous protein inhibitors (6), the latter being presented in more detail. CYSTEINE CATHEPSINS AND LEGUMAIN AS REGULATORS OF THE IMMUNE RESPONSEIn humans, cysteine cathepsins comprise a group of 11 lysosomal peptidases (cathepsins B, C, F, H, K, L, O, S, V, X and W). They are members of the papain family, classified as clan CA (7). The expression pattern, levels, localization and specificities of cysteine cathepsins differ, contributing to their various physiological roles. Cathepsins B, H, L and C are expressed ubiquitously in cells and tissues, while expression of others is restricted to specific cell types. They are endopeptidases, with the exception of cathepsins B, C, H and X. Cathepsins B and X are carboxypeptidases, cleaving substrates at the C-terminal end, while cathepsins B and H are aminopeptidases, cleaving substrates at the N-terminal end. Interestingly, in addition to exopeptidase activity, cathepsins B and H also exhibit endopeptidase activity (7,8). Cathepsin B can act as an endo-or exopeptidase due to the position of the structural element, termed the occluding loop, while in cathepsin H the type of activity is determined by a minicha...

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“…HEI was purified as described by Jarvinen (1978)-The protein concentration of the HEI antigen solution was 16-21 /^g/ml by the Lowry method (Lowry et al,195 0-The preparation was stored at -20 C until used. Analytical isoelectrofocusing, preparative isoelectrofocusing and PAGE of the purified HEI preparation revealed two protein bands which both possessed inhibitory activity.…”

Section: Preparation Of Epidermal Protease Inhibitormentioning

confidence: 99%

“…about 13,000, was demonstrated to be located in the epidermis and that with the higher molecular weight, i.e. about 74,000, in the dermis (Jarvinen, 1978). A similar low molecular weight inhibitor in human skin (HEI) (Fraki 1976, Jarvinen, 1978 is detectable in the keratinising cells of human epidermis and ofthe other epithelia but not in other tissues (Rasanen, Jarvinen & Rinne, 1978).…”

mentioning

confidence: 96%

“…about 74,000, in the dermis (Jarvinen, 1978). A similar low molecular weight inhibitor in human skin (HEI) (Fraki 1976, Jarvinen, 1978 is detectable in the keratinising cells of human epidermis and ofthe other epithelia but not in other tissues (Rasanen, Jarvinen & Rinne, 1978). The inhibitor both in rat and human epidermis is very soluble and antigenic and, therefore, it is possible that it could stimulate formation of autoantibodies in disease conditions involving keratinizing epithelia.…”

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confidence: 99%

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Autoantibodies to an epidermal protease inhibitor in skin diseases

1981

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Solid phase radioimmunoassay for measurement of autoantibodies in human sera to an epidermal protein is presented. The protein purified from normal human epidermis is inhibitory to SH-dependent protease and its molecular weight is about 13,000. Antibodies were detected in 139 of the 4,400 sera collected from dermatological patients. Most of the patients suffered from wide-spread eczematous conditions. It is suggested that the antibodies are secondary to the inflammatory conditions, but they may exacerbate or delay the course of the disease.

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Localization of the human SH-protease inhibitor in the epidermis

Cited by 29 publications

References 6 publications

Cystatins in Immune System

Cystatins in Immune System

Cystatins, cysteine peptidase inhibitors, as regulators of immune cell cytotoxicity

Autoantibodies to an epidermal protease inhibitor in skin diseases

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