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Tytuł:
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Caspofungin suppresses zymosan-induced cytokine and chemokine release in THP-1 cells: possible involvement of the spleen tyrosine kinase pathway.
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Autorzy:
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Itoh K; Department of Hematology and Oncology, Faculty of Medical Sciences, University of Fukui, Fukui, Japan; Division of Infection Control and Prevention, University of Fukui Hospital, Fukui, Japan. Electronic address: .
Shigemi H; Division of Infection Control and Prevention, University of Fukui Hospital, Fukui, Japan.
Chihara K; Department of Genome Science and Microbiology, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
Sada K; Department of Genome Science and Microbiology, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
Yamauchi T; Department of Hematology and Oncology, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
Iwasaki H; Division of Infection Control and Prevention, University of Fukui Hospital, Fukui, Japan.
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Źródło:
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Translational research : the journal of laboratory and clinical medicine [Transl Res] 2021 Jan; Vol. 227, pp. 53-63. Date of Electronic Publication: 2020 Jul 18.
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Original Publication: New York, N.Y. : Elsevier, [2006]-
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MeSH Terms:
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Adjuvants, Immunologic/*pharmacology
Antifungal Agents/*pharmacology
Caspofungin/*pharmacology
Chemokines/*metabolism
Cytokines/*metabolism
Protein-Tyrosine Kinases/*metabolism
Spleen/*enzymology
Zymosan/*pharmacology
Humans ; Signal Transduction ; THP-1 Cells
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Substance Nomenclature:
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0 (Adjuvants, Immunologic)
0 (Antifungal Agents)
0 (Chemokines)
0 (Cytokines)
9010-72-4 (Zymosan)
EC 2.7.10.1 (Protein-Tyrosine Kinases)
F0XDI6ZL63 (Caspofungin)
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Entry Date(s):
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Date Created: 20200721 Date Completed: 20210219 Latest Revision: 20210219
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Update Code:
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20240104
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DOI:
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10.1016/j.trsl.2020.07.005
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PMID:
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32687976
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Systemic inflammatory response syndrome and sepsis are considered to contribute to hypercytokinemia in both patients with severe infection and immunocompromised condition. Past research has demonstrated that antibiotics and antifungals not only have antimicrobial efficacy but also affect the immune system. We previously examined whether immune cells were modulated by antibiotics such as tetracyclines or macrolides. The modulation of lipopolysaccharide-stimulated cells by those agents was elucidated. However, few reports about the modulation of the immune system by antifungal agents were found. In this study, the production of pro-inflammatory cytokines and chemokines and signaling pathways involved were investigated in zymosan-activated THP-1 cells. The effects were examined using antifungal agents such as echinocandin including caspofungin (CAS) and micafungin. Pro-inflammatory cytokine and chemokine levels were determined using enzyme-linked immunosorbent assay. Protein phosphorylation was evaluated by western blot analysis. CAS significantly decreased zymosan-induced pro-inflammatory cytokine and chemokine release in THP-1 cells. CAS (30 µg/mL) also downregulated tumor necrosis factor alpha levels, as shown by enzyme-linked immunosorbent assay. In western blot analysis, inhibitor of nuclear factor-kappa-B alpha, p38, c-Jun N-terminal kinase, extracellular signal-regulated kinase, and nuclear factor of activated T-cells phosphorylation and activation of caspase-1 and spleen tyrosine kinase (Syk) were downregulated. The major underlying mechanism of pro-inflammatory cytokine and chemokine suppression by CAS is to inhibit activation of Syk and its downstream signaling molecules. Based on the results, it can be concluded that CAS activity possibly involves Syk signaling pathways and has potential to prevent hypercytokinemia in fungal sepsis.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
