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2025;2025 3430892.

-Mediated Reduction of Interleukin-1β Secretion and Its Association With Macrophage Autophagy.

Rachasak Boonhok, Wilaiwan Senghoi, Suthinee Sangkanu, Chooi Ling Lim, Matsayapan Pudla, Maria de Lourdes Pereira, Polrat Wilairatana, Tooba Mahboob, Md Atiar Rahman, Pongsak Utaisincharoen, Poonsit Hiransai, Veeranoot Nissapatorn
Author Information
  1. Rachasak Boonhok: Department of Medical Technology, School of Allied Health Sciences, and Research Excellence Center for Innovation and Health Products (RECIHP), Walailak University, Nakhon Si Thammarat 80160, Thailand. ORCID
  2. Wilaiwan Senghoi: Department of Medical Technology, School of Allied Health Sciences, and Center of Excellence Research for Melioidosis and Microorganisms (CERMM), Walailak University, Nakhon Si Thammarat 80160, Thailand. ORCID
  3. Suthinee Sangkanu: Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Songkhla 90112, Thailand. ORCID
  4. Chooi Ling Lim: Division of Applied Biomedical Science and Biotechnology, School of Health Sciences, International Medical University, Kuala Lumpur 57000, Malaysia. ORCID
  5. Matsayapan Pudla: Department of Oral Microbiology, Faculty of Dentistry, Mahidol University, Bangkok 10400, Thailand. ORCID
  6. Maria de Lourdes Pereira: CICECO-Aveiro Institute of Materials and Department of Medical Sciences, University of Aveiro, Aveiro 3810-193, Portugal. ORCID
  7. Polrat Wilairatana: Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand. ORCID
  8. Tooba Mahboob: Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur 56000, Malaysia. ORCID
  9. Md Atiar Rahman: Department of Biochemistry and Molecular Biology, University of Chittagong, Chittagong 4331, Bangladesh. ORCID
  10. Pongsak Utaisincharoen: Department of Microbiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand. ORCID
  11. Poonsit Hiransai: Department of Medical Technology, School of Allied Health Sciences, and Center of Excellence in Marijuana, Hemp, and Kratom, Walailak University, Nakhon Si Thammarat 80160, Thailand. ORCID
  12. Veeranoot Nissapatorn: School of Allied Health Sciences, Southeast Asia Water Team (SEA Water Team) and World Union for Herbal Drug Discovery (WUHeDD), Walailak University, Nakhon Si Thammarat 80160, Thailand. ORCID
PMID: 40109888 DOI: 10.1155/sci5/3430892

Abstract

Noncanonical autophagy including unconventional protein secretion has been extensively studied. Our work focused on a leaderless IL-1β protein secretion from human macrophage in response to components, culture supernatant (CS) and cell lysate (CL), as well as its association with macrophage autophagy. Phorbol 12-myristate 13-acetate (PMA)-induced THP-1 macrophages were treated with components of pathogenic (ATCC50739) and nonpathogenic (ATCC30010) strains in vitro. The data showed that treatment resulted in low IL-1β secretion from macrophages. In addition, CL of both strains was able to upregulate autophagy-related (Atg) protein 8, an autophagy marker, whereas CS downregulated Atg8 expression. We further manipulated autophagy and found that autophagy induction by starvation diminished IL-1β secretion while autophagy inhibition by 3-methyladenine (3MA) increased IL-1β secretion. Interestingly, in the presence of components either under starvation or 3MA treatment, IL-1β secretion was significantly reduced. Transcriptional expression of other ATG genes, i.e., ATG6, ATG7, and ATG5, were investigated and showed that their mRNA expression was maintained at the basal level under CS or CL treatment. Inflammasome-related genes, NLRP3 and CASPASE1, were upregulated following 50739 CS treatment but not in 50739 CL-treated condition. However, both conditions were able to increase IL-1β mRNA expression. TEM micrographs revealed that 3MA treatment induced the formation of large vacuoles and accumulation of autophagosome at the edge of THP-1 macrophages. However, the number and size of their structures were declined in the presence of 50739 CS with 3MA. Furthermore, immunofluorescence staining demonstrated the association between Atg8/LC3 and IL-1β expression, where downregulation of Atg8 by 50739 CS led to the upregulation of IL-1β. Altogether, the data indicate that can manipulate macrophage autophagy, thereby controlling low IL-1β secretion. The expression of autophagy- and inflammasome-related genes also indicates multiple mechanisms in IL-1β secretion in response to components. However, further characterization of Atg proteins and investigations into other intracellular pathways or defense mechanisms are needed to fully understand the unconventional secretion of IL-1β in macrophages. This knowledge could eventually lead to the development of innovative therapeutic strategies against infection by modulating autophagy or macrophage responses.

Keywords

Acanthamoeba castellanii autophagy human macrophage inflammasome interleukin-1β

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