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Annexin 1 cleavage in activated neutrophils: a pivotal role for proteinase 3.

ABSTRACT: Annexin 1 is an anti-inflammatory protein that plays a key role in innate immunity by modulating the activation of several types of cells, including neutrophils. Here we have developed a cleavage assay using tagged annexin 1 and observed marked activity in the membrane fraction of activated neutrophils. A combination of inhibitors, transfected cells, and proteomic analyses allowed us to identify proteinase 3 as the main enzyme responsible for this cleavage in the N terminus region of the protein, at least in the context of neutrophil activation. Because annexin 1 is an important endogenous anti-inflammatory mediator, blocking its cleavage by proteinase 3 would augment its homeostatic pro-resolving actions and could represent an opportunity for innovative anti-inflammatory drug discovery.

SUBMITTER: Vong L

PROVIDER: S-EPMC2772024 | biostudies-literature | 2007 Oct

REPOSITORIES: biostudies-literature

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Annexin 1 cleavage in activated neutrophils: a pivotal role for proteinase 3.

Vong Linda L D'Acquisto Fulvio F Pederzoli-Ribeil Magali M Lavagno Luisa L Flower Roderick J RJ Witko-Sarsat Véronique V Perretti Mauro M

The Journal of biological chemistry 20070806 41

Annexin 1 is an anti-inflammatory protein that plays a key role in innate immunity by modulating the activation of several types of cells, including neutrophils. Here we have developed a cleavage assay using tagged annexin 1 and observed marked activity in the membrane fraction of activated neutrophils. A combination of inhibitors, transfected cells, and proteomic analyses allowed us to identify proteinase 3 as the main enzyme responsible for this cleavage in the N terminus region of the protein ...[more]

PMID: 17681950

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Immunomodulatory role of proteinase-activated receptor-2.

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Role of Annexin A1 in NLRP3 Inflammasome Activation in Murine Neutrophils.

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Regulatory Network of Inflammation Downstream Proteinase-Activated Receptors

Project description:Here, cDNA array experiments determined inflammatory genes whose expression is dependent on PAR1 activation. For this purpose, we compared the alteration in gene expression in wild type and PAR1-/- mice induced by classical pro-inflammatory stimuli (LPS, SP, and antigen). 75 transcripts were considered to be dependent on PAR-1 activation and further annotated in silico by Ingenuity Pathways Analysis and gene ontology (GO). Selected transcripts were target validated by real-time PCR. Among PAR1-dependent transcripts, the following have been implicated in the inflammatory process: b2m, ccl7, cd200, cd63, cdbpd, cfl1, dusp1, fkbp1a, fth1, hspb1, marcksl1, mmp2, myo5a, nfkbia, pax1, plaur, ppia, ptpn1, ptprcap, s100a10, sim2, and tnfaip2. However, a balanced response to signals of injury requires a transient cellular activation of a panel of genes together with inhibitory systems which temper the overwhelming inflammation. In this context, the activation of genes such as dusp1 and nfkbia seems to counter-balance the inflammatory response to PAR activation by avoiding prolonged activation of p38 MAPK and increased cytokine production. In contrast, transcripts such as arf6 and dcnt1 that are involved in the mechanism of PAR re-sensitization would tend to perpetuate the inflammatory reaction in response to common pro-inflammatory stimuli. Keywords: time course, stress response, genetic modification

2006-11-29 | GSE6286 | GEO

Proteinase K digestion of Annexin A11 fibrils

Project description:Human Annexin A11 (Uniprot accession no. P50995) head domain (residues 2-196) was recombinantly expressed, purified, fibrilized, and digested by proteinase K. Products were analyzed by LC/MS/MS.

2023-01-20 | MSV000091107 | MassIVE

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