Anniina Pirttiniemi, Krishna Adeshara, Natalie Happonen, Elisabet Einarsdottir, Shintaro Katayama, Hanne Salmenkari, Sohvi Hörkkö, Juha Kere, Per-Henrik Groop, Markku Lehto, Long-chain polyphosphates inhibit type I interferon signaling and augment LPS-induced cytokine secretion in human leukocytes, Journal of Leukocyte Biology, Volume 114, Issue 3, September 2023, Pages 250–265, https://doi.org/10.1093/jleuko/qiad058.
Long-chain polyphosphates inhibit type I interferon signaling and augment LPS-induced cytokine secretion in human leukocytes
|Author:||Pirttiniemi, Anniina1,2,3; Adeshara, Krishna1,2,3; Happonen, Natalie4,5,6;|
1Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum, Haartmaninkatu 8, 00290 Helsinki, Finland
2Department of Nephrology, University of Helsinki and Helsinki University Hospital, Haartmaninkatu 4, 00290 Helsinki, Finland
3Clinical and Molecular Metabolism, Faculty of Medicine Research Programs, University of Helsinki, Biomedicum, Haartmaninkatu 8, 00290 Helsinki, Finland
4Medical Microbiology and Immunology, Research Unit of Biomedicine, University of Oulu, Aapistie 5A, 90220 Oulu, Finland
5Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Aapistie 5A, 90220 Oulu, Finland
6Nordlab, Oulu University Hospital, Kajaanintie 50, 90220 Oulu, Finland
7Science for Life Laboratory, Department of Gene Technology, KTH-Royal Institute of Technology, Tomtebodavägen 23A, 17165 Solna, Sweden
8Stem Cells and Metabolism Research Program, University of Helsinki, Biomedicum, Haartmaninkatu 8, 00290 Helsinki, Finland
9Department of Biosciences and Nutrition, Karolinska Institutet, Neo, Blickagången 16, Flemingsberg, SE-14183 Huddinge, Sweden
10Department of Diabetes, Central Clinical School, Monash University, Alfred Centre, 99 Commercial Road, Melbourne 3004, VIC, Australia
|Online Access:||PDF Full Text (PDF, 3.1 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe20231106143276
Oxford University Press,
|Publish Date:|| 2023-11-06
Inorganic polyphosphates are evolutionarily conserved bioactive phosphate polymers found as various chain lengths in all living organisms. In mammals, polyphosphates play a vital role in the regulation of cellular metabolism, coagulation, and inflammation. Long-chain polyphosphates are found along with endotoxins in pathogenic gram-negative bacteria and can participate in bacterial virulence. We aimed to investigate whether exogenously administered polyphosphates modulate human leukocyte function in vitro by treating the cells with 3 different chain lengths of polyphosphates (P14, P100, and P700). The long-chain polyphosphates, P700, had a remarkable capacity to downregulate type I interferon signaling dose dependently in THP1-Dual cells while only a slight elevation could be observed in the NF-κB pathway with the highest dose of P700. P700 treatment decreased lipopolysaccharide-induced IFNβ transcription and secretion, reduced STAT1 phosphorylation, and downregulated subsequent interferon-stimulated gene expression in primary human peripheral blood mononuclear cells. P700 also augmented lipopolysaccharide-induced secretion of IL-1α, IL-1β, IL-4, IL-5, IL-10, and IFNγ. Furthermore, P700 has previously been reported to increase the phosphorylation of several intracellular signaling mediators, such as AKT, mTOR, ERK, p38, GSK3α/β, HSP27, and JNK pathway components, which was supported by our findings. Taken together, these observations demonstrate the extensive modulatory effects P700 has on cytokine signaling and the inhibitory effects specifically targeted to type I interferon signaling in human leukocytes.
Journal of leukocyte biology
|Pages:||250 - 265|
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
This work was supported by following funding sources: Folkhälsan Research Foundation, Academy of Finland [275614, 316664], Novo Nordisk Foundation [NNF OC0013659], Helsinki University Hospital Research Funds, Wilhelm and Else Stockmann Foundation (PHG), Sigrid Jusélius Foundation (J.K.), Jane and Aatos Erkko Foundation (S.K.) and University of Helsinki; The Doctoral School in Health Sciences; and The Doctoral Programme in Clinical Research (A.P.).
© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Leukocyte Biology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.