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  1. Article ; Online: Circulating heat shock protein 90 (Hsp90) in atopic dermatitis and bullous pemphigoid: is there a link?

    Tukaj, Stefan

    Cell stress & chaperones

    2022  Volume 27, Issue 6, Page(s) 601–602

    MeSH term(s) Humans ; Pemphigoid, Bullous/metabolism ; Dermatitis, Atopic ; HSP90 Heat-Shock Proteins/metabolism ; Autoantibodies
    Chemical Substances HSP90 Heat-Shock Proteins ; Autoantibodies
    Language English
    Publishing date 2022-09-23
    Publishing country Netherlands
    Document type Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 1362749-1
    ISSN 1466-1268 ; 1355-8145
    ISSN (online) 1466-1268
    ISSN 1355-8145
    DOI 10.1007/s12192-022-01298-6
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4797: Show issues Location:
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  2. Article ; Online: Heat Shock Protein 70 as a Double Agent Acting Inside and Outside the Cell: Insights into Autoimmunity.

    Tukaj, Stefan

    International journal of molecular sciences

    2020  Volume 21, Issue 15

    Abstract: Heat shock proteins (Hsp) are a diverse group of constitutive and/or stress-induced molecules that are categorized into several classes on the basis of their molecular weight. Mammalian Hsp have been mostly regarded as intracellular chaperones that ... ...

    Abstract Heat shock proteins (Hsp) are a diverse group of constitutive and/or stress-induced molecules that are categorized into several classes on the basis of their molecular weight. Mammalian Hsp have been mostly regarded as intracellular chaperones that mediate a range of essential cellular functions, including proper folding of newly synthesized polypeptides, refolding of denatured proteins, protein transport, and stabilization of native proteins' structures. The well-characterized and highly evolutionarily conserved, stress-inducible 70-kDa heat shock protein (Hsp70), is a key molecular chaperone that is overexpressed in the cell in response to stress of various origin. Hsp70 exhibits an immunosuppressive activity via, e.g., downregulation of the nuclear factor-kappa B (NF-κB) activation, and pharmacological induction of Hsp70 can ameliorate the autoimmune arthritis development in animal models. Moreover, Hsp70 might be passively or actively released from the necrotic or stressed cells, respectively. Highly immunogenic extracellular Hsp70 has been reported to impact both the innate and adaptive immune responses, and to be implicated in the autoimmune reaction. In addition, preclinical studies revealed that immunization with highly conserved Hsp70 peptides could be regarded as a potential treatment target for autoimmune arthritis, such as the rheumatoid arthritis, via induction of antigen-specific regulatory T helper cells (also called Treg). Here, a dual role of the intra- and extracellular Hsp70 is presented in the context of the autoimmune reaction.
    MeSH term(s) Adaptive Immunity ; Animals ; Arthritis, Rheumatoid/immunology ; Arthritis, Rheumatoid/pathology ; Down-Regulation/immunology ; HSP70 Heat-Shock Proteins/immunology ; Humans ; Immunity, Innate ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/pathology
    Chemical Substances HSP70 Heat-Shock Proteins
    Language English
    Publishing date 2020-07-26
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms21155298
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  3. Article ; Online: Vitamin D in autoimmune bullous disease.

    Tukaj, Stefan

    Acta biochimica Polonica

    2020  Volume 67, Issue 1, Page(s) 1–5

    Abstract: Numerous epidemiological studies have suggested a link between vitamin D deficiency and the development of various autoimmune diseases, including diabetes mellitus type 1, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis or systemic ... ...

    Abstract Numerous epidemiological studies have suggested a link between vitamin D deficiency and the development of various autoimmune diseases, including diabetes mellitus type 1, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis or systemic lupus erythematosus. More recently, such a link has been also proposed for autoimmune bullous diseases (AIBD). This is a relatively rare and potentially life-threatening, organ-specific group of inflammatory skin diseases characterized by the presence of tissue-bound and circulating autoantibodies against various molecules present in desmosomes (in pemphigus diseases) or hemidesmosomes (in pemphigoid diseases). In addition to the well-known role of vitamin D in calcium and phosphate homeostasis, the hormonally active vitamin D metabolite, 1,25-dihydroxyvitamin D3 (calcitriol), exerts potent effects on cellular differentiation and regulation of immune responses via binding to the vitamin D receptor present in most cells of the immune system. Since cells of both, the innate and adaptive immune systems, are known to be relevant in AIBD, the role of vitamin D analogues in the treatment of patients with these disorders deserves much attention. This mini-review summarizes recent epidemiological and experimental studies on vitamin D involvement in the autoimmune bullous diseases.
    MeSH term(s) Autoimmune Diseases/drug therapy ; Humans ; Skin Diseases, Vesiculobullous/drug therapy ; Skin Diseases, Vesiculobullous/immunology ; Vitamin D/analogs & derivatives ; Vitamin D/therapeutic use
    Chemical Substances Vitamin D (1406-16-2)
    Language English
    Publishing date 2020-02-07
    Publishing country Poland
    Document type Journal Article ; Review
    ZDB-ID 595762-x
    ISSN 1734-154X ; 0001-527X
    ISSN (online) 1734-154X
    ISSN 0001-527X
    DOI 10.18388/abp.2020_2905
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    In stock of ZB MED Cologne/Königswinter

    Zs.B 232: Show issues Location:
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  4. Article: Commentary: Bullous pemphigoid associated with COVID-19 vaccines: An Italian multicenter study.

    Kasperkiewicz, Michael / Tukaj, Stefan

    Frontiers in medicine

    2022  Volume 9, Page(s) 1096867

    Language English
    Publishing date 2022-12-19
    Publishing country Switzerland
    Document type Journal Article ; Comment
    ZDB-ID 2775999-4
    ISSN 2296-858X
    ISSN 2296-858X
    DOI 10.3389/fmed.2022.1096867
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  5. Article ; Online: Heat Shock Protein 70 as a Double Agent Acting Inside and Outside the Cell

    Stefan Tukaj

    International Journal of Molecular Sciences, Vol 21, Iss 5298, p

    Insights into Autoimmunity

    2020  Volume 5298

    Abstract: Heat shock proteins (Hsp) are a diverse group of constitutive and/or stress-induced molecules that are categorized into several classes on the basis of their molecular weight. Mammalian Hsp have been mostly regarded as intracellular chaperones that ... ...

    Abstract Heat shock proteins (Hsp) are a diverse group of constitutive and/or stress-induced molecules that are categorized into several classes on the basis of their molecular weight. Mammalian Hsp have been mostly regarded as intracellular chaperones that mediate a range of essential cellular functions, including proper folding of newly synthesized polypeptides, refolding of denatured proteins, protein transport, and stabilization of native proteins’ structures. The well-characterized and highly evolutionarily conserved, stress-inducible 70-kDa heat shock protein (Hsp70), is a key molecular chaperone that is overexpressed in the cell in response to stress of various origin. Hsp70 exhibits an immunosuppressive activity via, e.g., downregulation of the nuclear factor-kappa B (NF-κB) activation, and pharmacological induction of Hsp70 can ameliorate the autoimmune arthritis development in animal models. Moreover, Hsp70 might be passively or actively released from the necrotic or stressed cells, respectively. Highly immunogenic extracellular Hsp70 has been reported to impact both the innate and adaptive immune responses, and to be implicated in the autoimmune reaction. In addition, preclinical studies revealed that immunization with highly conserved Hsp70 peptides could be regarded as a potential treatment target for autoimmune arthritis, such as the rheumatoid arthritis, via induction of antigen-specific regulatory T helper cells (also called Treg). Here, a dual role of the intra- and extracellular Hsp70 is presented in the context of the autoimmune reaction.
    Keywords Heat shock proteins ; Hsp ; Hsp70 ; autoimmune diseases ; inflammation ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 616
    Language English
    Publishing date 2020-07-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Heat Shock Protein 90 (Hsp90) and Hsp70 as Potential Therapeutic Targets in Autoimmune Skin Diseases.

    Tukaj, Stefan / Sitko, Krzysztof

    Biomolecules

    2022  Volume 12, Issue 8

    Abstract: Over a hundred different autoimmune diseases have been described to date, which can affect every organ in the body, including the largest one, the skin. In fact, up to one-fifth of the world's population suffers from chronic, noninfectious inflammatory ... ...

    Abstract Over a hundred different autoimmune diseases have been described to date, which can affect every organ in the body, including the largest one, the skin. In fact, up to one-fifth of the world's population suffers from chronic, noninfectious inflammatory skin diseases, the development of which is significantly influenced by an autoimmune response. One of the hallmarks of autoimmune diseases is the loss of immune tolerance, which leads to the formation of autoreactive lymphocytes or autoantibodies and, consequently, to chronic inflammation and tissue damage. The treatment of autoimmune skin diseases mainly focuses on immunosuppression (using, e.g., corticosteroids) but almost never leads to the development of permanent mechanisms of immune tolerance. In addition, current therapies and their long-term administration may cause serious adverse effects. Hence, safer and more effective therapies that bring sustained balance between pro- and anti-inflammatory responses are still desired. Both intra- and extracellular heat shock proteins (Hsps), specifically well-characterized inducible Hsp90 and Hsp70 chaperones, have been highlighted as therapeutic targets for autoimmune diseases. This review presents preclinical data on the involvement of Hsp90 and Hsp70 in modulating the immune response, specifically in the context of the treatment of selected autoimmune skin diseases with emphasis on autoimmune bullous skin diseases and psoriasis.
    MeSH term(s) Autoimmune Diseases/drug therapy ; HSP70 Heat-Shock Proteins/metabolism ; HSP90 Heat-Shock Proteins/metabolism ; Heat-Shock Proteins/metabolism ; Humans ; Skin Diseases/drug therapy
    Chemical Substances HSP70 Heat-Shock Proteins ; HSP90 Heat-Shock Proteins ; Heat-Shock Proteins
    Language English
    Publishing date 2022-08-20
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2701262-1
    ISSN 2218-273X ; 2218-273X
    ISSN (online) 2218-273X
    ISSN 2218-273X
    DOI 10.3390/biom12081153
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  7. Article ; Online: Heat shock protein 90 (Hsp90) inhibitor STA-9090 (Ganetespib) ameliorates inflammation in a mouse model of atopic dermatitis.

    Sitko, Krzysztof / Starke, Michał / Tukaj, Stefan

    Cell stress & chaperones

    2023  Volume 28, Issue 6, Page(s) 935–942

    Abstract: Molecular chaperones belonging to the heat shock protein 90 (Hsp90) family are implicated in inflammatory processes and described as potential novel therapeutic targets in autoimmune/inflammatory skin diseases. While the pathological role of circulating ... ...

    Abstract Molecular chaperones belonging to the heat shock protein 90 (Hsp90) family are implicated in inflammatory processes and described as potential novel therapeutic targets in autoimmune/inflammatory skin diseases. While the pathological role of circulating Hsp90 has been recently proposed in patients with atopic dermatitis (AD), a chronic inflammatory skin disease characterized by intense itching and recurrent skin lesions, studies aimed at investigating the role of Hsp90 as a potential target of AD therapy have not yet been conducted. Here, the effects of the Hsp90 blocker STA-9090 (Ganetespib) applied systemically or topically were determined in an experimental mouse model of dinitrochlorobenzene (DNCB)-induced AD. Intraperitoneal administration of STA-9090 ameliorated clinical disease severity, histological epidermal thickness, and dermal leukocyte infiltration in AD mice which was associated with reducing the scratching behavior in DNCB-treated animals. Additionally, topically applied STA-9090 led to lowered disease activity in AD mice, reduced serum levels of IgE, and up-regulated filaggrin expression in lesional skin samples. Our observations suggest that Hsp90 may be a promising therapeutic target in atopic dermatitis and potentially other inflammatory or autoimmune dermatoses.
    MeSH term(s) Humans ; Animals ; Mice ; Dermatitis, Atopic ; Dinitrochlorobenzene/metabolism ; Dinitrochlorobenzene/pharmacology ; Dinitrochlorobenzene/therapeutic use ; Immunoglobulin E ; Skin/metabolism ; Inflammation/metabolism ; Antineoplastic Agents/pharmacology ; Heat-Shock Proteins/metabolism ; Cytokines/metabolism ; Mice, Inbred BALB C
    Chemical Substances STA 9090 ; Dinitrochlorobenzene ; Immunoglobulin E (37341-29-0) ; Antineoplastic Agents ; Heat-Shock Proteins ; Cytokines
    Language English
    Publishing date 2023-10-18
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1362749-1
    ISSN 1466-1268 ; 1355-8145
    ISSN (online) 1466-1268
    ISSN 1355-8145
    DOI 10.1007/s12192-023-01387-0
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4797: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  8. Article: Differences in the detection of circulating Hsp90 alpha between patients with atopic dermatitis and dermatitis herpetiformis.

    Sitko, Krzysztof / Kárpáti, Sarolta / Węgrzyn, Grzegorz / Mincewicz, Grzegorz / Trzeciak, Magdalena / Kasperkiewicz, Michael / Tukaj, Stefan

    Frontiers in medicine

    2024  Volume 10, Page(s) 1327144

    Abstract: Heat shock protein 90 alpha (Hsp90α) is one of the key intra- and extracellular chaperones responsible for the biological activity of various signaling molecules that are involved in (auto)immune-mediated inflammatory diseases. Recent epidemiologic data ... ...

    Abstract Heat shock protein 90 alpha (Hsp90α) is one of the key intra- and extracellular chaperones responsible for the biological activity of various signaling molecules that are involved in (auto)immune-mediated inflammatory diseases. Recent epidemiologic data suggest that patients with atopic dermatitis (AD) are at risk for several autoimmune diseases, including dermatitis herpetiformis (DH), an extraintestinal manifestation of celiac disease (CD). In addition, pruritic diseases such as AD may be confused clinically with DH. In this study, we aimed to determine the role of circulating Hsp90α in patients with AD in relation to patients with DH, CD, and healthy controls. Using an enzyme-linked immunosorbent assay, levels of circulating Hsp90α were determined in serum samples derived from patients with AD (
    Language English
    Publishing date 2024-01-05
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2775999-4
    ISSN 2296-858X
    ISSN 2296-858X
    DOI 10.3389/fmed.2023.1327144
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  9. Article ; Online: Altered Gene Expression of IL-35 and IL-36α in the Skin of Patients with Atopic Dermatitis.

    Zysk, Weronika / Sitko, Krzysztof / Tukaj, Stefan / Zaryczańska, Anna / Trzeciak, Magdalena

    International journal of molecular sciences

    2023  Volume 25, Issue 1

    Abstract: A comprehensive understanding of atopic dermatitis (AD) pathogenesis is desired, especially in the current era of novel biologics and small molecule drugs. In recent years, new cytokines have emerged that may play a significant role in the pathogenesis ... ...

    Abstract A comprehensive understanding of atopic dermatitis (AD) pathogenesis is desired, especially in the current era of novel biologics and small molecule drugs. In recent years, new cytokines have emerged that may play a significant role in the pathogenesis of AD. Using the tape stripping (TS) method, this study analyzed the gene expression of IL-35 and IL-36α in lesional and nonlesional AD skin compared with healthy skin and their association with the clinical features of AD among the Polish population. Ten AD patients and seven healthy individuals were enrolled. The lesional skin of the AD patients showed significantly higher expression levels of IL-35 compared to healthy skin (
    MeSH term(s) Humans ; Biological Products ; Dermatitis, Atopic/genetics ; Gene Expression ; Interleukins/genetics ; Skin
    Chemical Substances Biological Products ; Interleukins ; IL12A protein, human ; IL36A protein, human
    Language English
    Publishing date 2023-12-28
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms25010404
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  10. Article ; Online: Immunoregulacyjne właściwości białek Hsp70.

    Tukaj, Stefan

    Postepy higieny i medycyny doswiadczalnej (Online)

    2014  Volume 68, Page(s) 722–727

    Abstract: Heat shock proteins 70 (Hsp70) play an important role in maintaining cellular homeostasis. As molecular chaperones, Hsp70 are responsible for proper folding of newly synthesized polypeptides and refolding of misfolded and aggregated proteins. Hsp70 are ... ...

    Title translation Immunoregulatory properties of Hsp70.
    Abstract Heat shock proteins 70 (Hsp70) play an important role in maintaining cellular homeostasis. As molecular chaperones, Hsp70 are responsible for proper folding of newly synthesized polypeptides and refolding of misfolded and aggregated proteins. Hsp70 are involved in cellular transport and participate in signal transduction processes. The presence of Hsp70 in the extracellular space is associated with development of various pathological conditions, including autoimmune and cancer diseases. Recent data suggest anti-inflammatory property of Hsp70 confirmed in both in vitro and animal models. This paper summarizes recent data regarding immunoregulatory properties of Hsp70, and presents promising results of the studies concerning the application of heat shock proteins in treatment of chronic inflammatory diseases.
    MeSH term(s) Animals ; Autoimmune Diseases/immunology ; Disease Models, Animal ; Extracellular Space/immunology ; HSP70 Heat-Shock Proteins/immunology ; HSP70 Heat-Shock Proteins/therapeutic use ; Homeostasis/physiology ; Humans ; Inflammation/drug therapy ; Molecular Chaperones/metabolism ; Neoplasms/immunology ; Peptides/chemistry ; Protein Folding ; Signal Transduction/physiology
    Chemical Substances HSP70 Heat-Shock Proteins ; Molecular Chaperones ; Peptides
    Language Polish
    Publishing date 2014-06-05
    Publishing country Poland
    Document type Journal Article ; Review
    ZDB-ID 418865-2
    ISSN 1732-2693 ; 0032-5449
    ISSN (online) 1732-2693
    ISSN 0032-5449
    DOI 10.5604/17322693.1107329
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.B 634: Show issues Location:
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