Dataset Information

Proteomics of THP-1 macrophages polarization to M1 and M2 phenotype and treated with BB-Cl-amidine

ABSTRACT: Macrophages are effector cells of the innate immune system and undergo phenotypical changes in response to organ injury and repair. They are most often classified as proinflammatory M1 and anti-inflammatory M2 macrophages. Protein arginine deiminase (PAD) enzymes, that catalyze the conversion of protein-bound arginine into citrulline, an irreversible posttranslational modification, are expressed in macrophages. However, the substrate scope of the PADs and their role in the immune cells remain not well defined. This study aims to investigate the role of PADs in the THP-1 macrophage polarization to M1 and M2 phenotype and identify the citrullinated proteins, and the modified Arg that are associated with this biological switch using mass spectrometry. Our study showed that PAD2, and to a lesser extent PAD1 and PAD4 were dominantly expressed in M1 macrophages. We showed that inhibiting PADs by BB-Cl-amidine decreased the macrophage’s polarization to M1 and increased to M2 phenotype. The process was mediated by the downregulation of proteins involved in NF-kβ pathway. Silencing of PAD2 confirmed activation to M2 macrophages through upregulation of the antiviral innate immune response and interferon signaling. 192 novel citrullination sites that belong to inflammation, cell death and DNA/RNA processing pathways were identified in M1 and M2 macrophages.

INSTRUMENT(S): TripleTOF 6600

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Macrophage

SUBMITTER: Maciej Suski

LAB HEAD: Justyna Fert-Bober

PROVIDER: PXD034591 | Pride | 2023-03-11

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20210819_152440_THP-1_macrophages_PAD2KO_PAD2KO_library.sne	Other
	20210930_163125_THP-1_macrophages_M1_M2activation_plus_BB-Cl_USA_library.sne	Other
	F1_I_PAD-_powt.wiff	Wiff
	F1_I_PAD-_powt.wiff.scan	Wiff
	F1_I_PAD_powt.wiff	Wiff

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Publications

Protein arginine deiminase 2 (PAD2) modulates the polarization of THP-1 macrophages to the anti-inflammatory M2 phenotype.

Stachowicz Aneta A Pandey Rakhi R Sundararaman Niveda N Venkatraman Vidya V Van Eyk Jennifer E JE Fert-Bober Justyna J

Journal of inflammation (London, England) 20221118 1

<h4>Background</h4>Macrophages are effector cells of the innate immune system that undergo phenotypical changes in response to organ injury and repair. These cells are most often classified as proinflammatory M1 and anti-inflammatory M2 macrophages. Protein arginine deiminase (PAD), which catalyses the irreversible conversion of protein-bound arginine into citrulline, is expressed in macrophages. However, the substrates of PAD and its role in immune cells remain unclear. This study aimed to inve ...[more]

PMID: 36401289

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