Gram-negative bacteria-driven increase of cytosolic phospholipase A2 leads to activation of Kupffer cells.

Autor: Lin H; Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China. swlinhao@163.com.; Department of Medicine II, University Hospital, Liver Centre Munich, LMU Munich, Munich, Germany. swlinhao@163.com., Wieser A; Medical Microbiology and Hospital Epidemiology, Faculty of Medicine, Max von Pettenkofer Institute, LMU Munich, Munich, Germany.; Division of Infectious Diseases and Tropical Medicine, University Hospital, LMU Munich, Munich, Germany.; German Center for Infection Research (DZIF), Partner Site Munich, Munich, Germany., Zhang J; Department of Liver Surgery and Liver Transplantation Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China., Regel I; Department of Medicine II, University Hospital, Liver Centre Munich, LMU Munich, Munich, Germany., Nieß H; Department of General, Visceral and Transplant Surgery, University Hospital, LMU Munich, Munich, Germany., Mayerle J; Department of Medicine II, University Hospital, Liver Centre Munich, LMU Munich, Munich, Germany., Gerbes AL; Department of Medicine II, University Hospital, Liver Centre Munich, LMU Munich, Munich, Germany., Liu S; Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China. liuside2011@163.com., Steib CJ; Department of Internal Medicine and Gastroenterology, Internistisches Klinikum München Süd, Am Isarkanal 36, Munich, Germany. Christian.Steib@ikms.de.
Jazyk: angličtina
Zdroj: Cellular and molecular life sciences : CMLS [Cell Mol Life Sci] 2024 Dec 27; Vol. 82 (1), pp. 22. Date of Electronic Publication: 2024 Dec 27.
DOI: 10.1007/s00018-024-05451-5
Abstrakt: Bacterial infections are prevalent and the major cause of morbidity and mortality in cirrhosis. Activation of human Kupffer cells (HKCs) from livers is essential for human innate immunity. Cytosolic phospholipase A2 (cPLA2) plays a crucial role in the control and balance of innate immune and inflammatory reactions. Uncharacterized is the role of cPLA2 in HKC activation by bacterial infection. This work aimed to determine the function and mechanism of cPLA2 in gram-negative bacteria (GNB)-induced HKC activation. In this study, we found that Escherichia coli (E. coli)-induced activation of HKCs led to a rise in cPLA2 mRNA and protein expression, where the ERK and NF-κB pathways were concurrently triggered. Luciferase activity of cPLA2' promoters, PLA2G4A promoters, was enhanced with the stimulation of E. coli or co-transfection with STAT3 or RelB in HKCs. E. coli massively boosted the binding activity of STAT3 and RelB to the specific regions of the PLA2G4A promoter as measured by ChIP-qPCR. The E. coli-ERK-STAT3 and E. coli-non-canonical NF-κB-RelB signaling axes were then identified using pathway inhibitors and transcription factors in the rescue experiments during E. coli-induced HKC activation. In conclusion, we discovered that cPLA2 is necessary for E. coli-induced HKC activation, and the underlying mechanism could be the transcriptional regulation of STAT3 and RelB on the PLA2G4A promoter following the ERK and non-canonical NF-κB signaling activation, implying that the regulation of cPLA2 expression via the E. coli-ERK/non-canonical NF-κB-STAT3/RelB signaling axis could be effective for controlling GNB-induced HKC activation in cirrhotic patients.
Competing Interests: Declarations. Ethics approval and consent to participate: The framework of the HTCR Foundation has been approved by the ethics committee of the Faculty of Medicine at the LMU (approval number 025 − 12) as well as the Bavarian State Medical Association (approval number 11142) in Germany. Written informed consent has been obtained from the patient(s) to publish this paper. Consent for publication: Not applicable. Conflict of interest: The authors declare no conflict of interest.
(© 2024. The Author(s).)
Databáze: MEDLINE
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