Frontiers in Immunology (Mar 2023)
Proteomic characterisation of perhexiline treatment on THP-1 M1 macrophage differentiation
- Bimala Dhakal,
- Bimala Dhakal,
- Celine Man Ying Li,
- Celine Man Ying Li,
- Mahnaz Ramezanpour,
- Mahnaz Ramezanpour,
- Mahnaz Ramezanpour,
- Ghais Houtak,
- Ghais Houtak,
- Ghais Houtak,
- Runhao Li,
- Runhao Li,
- Runhao Li,
- George Bouras,
- George Bouras,
- George Bouras,
- Alex Collela,
- Nusha Chegeni,
- Tim Kennion Chataway,
- Paul Drew,
- Paul Drew,
- Benedetta C. Sallustio,
- Benedetta C. Sallustio,
- Sarah Vreugde,
- Sarah Vreugde,
- Sarah Vreugde,
- Eric Smith,
- Eric Smith,
- Eric Smith,
- Guy Maddern,
- Guy Maddern,
- Giovanni Licari,
- Giovanni Licari,
- Kevin Fenix,
- Kevin Fenix,
- Kevin Fenix
Affiliations
- Bimala Dhakal
- Discipline of Surgery, Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia
- Bimala Dhakal
- The Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, SA, Australia
- Celine Man Ying Li
- Discipline of Surgery, Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia
- Celine Man Ying Li
- The Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, SA, Australia
- Mahnaz Ramezanpour
- Discipline of Surgery, Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia
- Mahnaz Ramezanpour
- The Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, SA, Australia
- Mahnaz Ramezanpour
- Department of Surgery-Otolaryngology Head and Neck Surgery, Central Adelaide Local Health Network, Adelaide, SA, Australia
- Ghais Houtak
- Discipline of Surgery, Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia
- Ghais Houtak
- The Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, SA, Australia
- Ghais Houtak
- Department of Surgery-Otolaryngology Head and Neck Surgery, Central Adelaide Local Health Network, Adelaide, SA, Australia
- Runhao Li
- Discipline of Surgery, Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia
- Runhao Li
- The Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, SA, Australia
- Runhao Li
- Medical Oncology, The Queen Elizabeth Hospital, Adelaide, SA, Australia
- George Bouras
- Discipline of Surgery, Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia
- George Bouras
- The Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, SA, Australia
- George Bouras
- Department of Surgery-Otolaryngology Head and Neck Surgery, Central Adelaide Local Health Network, Adelaide, SA, Australia
- Alex Collela
- Flinders Omics Facility, Department of Human Physiology, Flinders University, Adelaide, SA, Australia
- Nusha Chegeni
- Flinders Omics Facility, Department of Human Physiology, Flinders University, Adelaide, SA, Australia
- Tim Kennion Chataway
- Flinders Omics Facility, Department of Human Physiology, Flinders University, Adelaide, SA, Australia
- Paul Drew
- Discipline of Surgery, Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia
- Paul Drew
- The Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, SA, Australia
- Benedetta C. Sallustio
- The Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, SA, Australia
- Benedetta C. Sallustio
- Discipline of Pharmacology, School of Biomedicine, The University of Adelaide, Adelaide, SA, Australia
- Sarah Vreugde
- Discipline of Surgery, Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia
- Sarah Vreugde
- The Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, SA, Australia
- Sarah Vreugde
- Department of Surgery-Otolaryngology Head and Neck Surgery, Central Adelaide Local Health Network, Adelaide, SA, Australia
- Eric Smith
- Discipline of Surgery, Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia
- Eric Smith
- The Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, SA, Australia
- Eric Smith
- Medical Oncology, The Queen Elizabeth Hospital, Adelaide, SA, Australia
- Guy Maddern
- Discipline of Surgery, Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia
- Guy Maddern
- The Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, SA, Australia
- Giovanni Licari
- The Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, SA, Australia
- Giovanni Licari
- Discipline of Pharmacology, School of Biomedicine, The University of Adelaide, Adelaide, SA, Australia
- Kevin Fenix
- Discipline of Surgery, Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia
- Kevin Fenix
- The Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, SA, Australia
- Kevin Fenix
- Department of Surgery-Otolaryngology Head and Neck Surgery, Central Adelaide Local Health Network, Adelaide, SA, Australia
- DOI
- https://doi.org/10.3389/fimmu.2023.1054588
- Journal volume & issue
-
Vol. 14
Abstract
BackgroundDysregulated inflammation is important in the pathogenesis of many diseases including cancer, allergy, and autoimmunity. Macrophage activation and polarisation are commonly involved in the initiation, maintenance and resolution of inflammation. Perhexiline (PHX), an antianginal drug, has been suggested to modulate macrophage function, but the molecular effects of PHX on macrophages are unknown. In this study we investigated the effect of PHX treatment on macrophage activation and polarization and reveal the underlying proteomic changes induced.MethodsWe used an established protocol to differentiate human THP-1 monocytes into M1 or M2 macrophages involving three distinct, sequential stages (priming, rest, and differentiation). We examined the effect of PHX treatment at each stage on the polarization into either M1 or M2 macrophages using flow cytometry, quantitative polymerase chain reaction (qPCR) and enzyme linked immunosorbent assay (ELISA). Quantitative changes in the proteome were investigated using data independent acquisition mass spectrometry (DIA MS).ResultsPHX treatment promoted M1 macrophage polarization, including increased STAT1 and CCL2 expression and IL-1β secretion. This effect occurred when PHX was added at the differentiation stage of the M1 cultures. Proteomic profiling of PHX treated M1 cultures identified changes in metabolic (fatty acid metabolism, cholesterol homeostasis and oxidative phosphorylation) and immune signalling (Receptor Tyrosine Kinase, Rho GTPase and interferon) pathways.ConclusionThis is the first study to report on the action of PHX on THP-1 macrophage polarization and the associated changes in the proteome of these cells.
Keywords
- M1 macrolphage
- perhexiline
- quantitative proteomics
- THP-1 derived macrophages
- macrophage polarisation
