Urokinase Plasminogen Activator and Plasmin Efficiently Convert Hemofiltrate CC Chemokine 1 into Its Active [9–74] Processed Variant

Vakili, Jalal; Ständker, Ludger; Detheux, Michel; Vassart, Gilbert; Forssmann, Wolf‐Georg; Parmentier, Marc

doi:10.4049/jimmunol.167.6.3406

Cited by 51 publications

(42 citation statements)

References 64 publications

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“…Chemokine activation after proteolytic removal of N-terminal residues has been described for two other CCR1 ligands, CCL14/HCC-1 (16,17) and the MIP-1␣ isoform LD78␤ (18), as well as for CXC chemokines CXCL1-3, -5, and -8 (19 -24). However, none of these chemokines possesses separately encoded, extended N-terminal domains, and all truncations were relatively small (Ͻ10 aa residues removed).…”

Section: Discussionmentioning

confidence: 99%

Proteolytic Activation of Alternative CCR1 Ligands in Inflammation

Berahovich

Miao

Wang

et al. 2005

The Journal of Immunology

154

130

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Although chemokines CCL3/MIP-1α and CCL5/RANTES are considered to be primary CCR1 ligands in inflammatory responses, alternative CCR1 ligands have also been described. Indeed, four such chemokines, CCL6/C10/MIP-related protein-1, CCL9/MIP-1γ/MIP-related protein-2, CCL15/MIP-1δ/hemofiltrate CC chemokine-2/leukotactin-1, and CCL23/CKβ8/myeloid progenitor inhibitory factor-1, are unique in possessing a separately encoded N-terminal domain of 16–20 residues and two additional precisely positioned cysteines that form a third disulfide bridge. In vitro, these four chemokines are weak CCR1 agonists, but potency can be increased up to 1000-fold by engineered or expression-associated N-terminal truncations. We examined the ability of proinflammatory proteases, human cell supernatants, or physiological fluids to perform N-terminal truncations of these chemokines and thereby activate their functions. Remarkably, most of the proteases and fluids removed the N-terminal domains from all four chemokines, but were relatively unable to cleave the truncated forms further. The truncated chemokines exhibited up to 1000-fold increases in CCR1-mediated signaling and chemotaxis assays in vitro. In addition, N-terminally truncated CCL15/MIP-1δ and CCL23/CKβ8, but not CCL3/MIP-1α or CCL5/RANTES, were detected at relatively high levels in synovial fluids from rheumatoid arthritis patients. These data suggest that alternative CCR1 ligands are converted into potent chemoattractants by proteases released during inflammatory responses in vivo.

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Section: Discussionmentioning

confidence: 99%

Proteolytic Activation of Alternative CCR1 Ligands in Inflammation

Berahovich

Miao

Wang

et al. 2005

The Journal of Immunology

154

130

View full text Add to dashboard Cite

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“…CCL14 is present in the blood as an inactive chemokine. It is proteolytically activated by serine proteases of the fibrinolytic cascade to a potent chemoattractant for CCR1/ CCR3/CCR5-expressing cells (26) and is then either further processed by CD26 or degraded by the scavenging receptor D6 (Fig. 7).…”

Section: Discussionmentioning

confidence: 99%

Recognition Versus Adaptive Up-regulation and Degradation of CC Chemokines by the Chemokine Decoy Receptor D6 Are Determined by Their N-terminal Sequence

Savino

Borroni

Torres

et al. 2009

Journal of Biological Chemistry

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The chemokine decoy receptor D6 controls inflammatory responses by selective recognition and degradation of most CCR1 to CCR5 agonistic ligands. CCL14 is a homeostatic chemokine present at high concentrations in the serum with a weak agonist activity on CCR1. Under inflammatory conditions, plasmin and UPA-mediated truncation of 8 amino acids generates the potent CCR1/CCR3/CCR5 isoform CCL14(9 -74), which is further processed and inactivated by dipeptidyl peptidase IV/CD26 that generates CCL14(11-74). Here we report that D6 efficiently binds both CCL14 and its truncated isoforms. Like other D6 ligands, the biologically active CCL14(9 -74) induces adaptive up-regulation of D6 expression on the cell membrane and is rapidly and efficiently degraded. In contrast, the D6-mediated degradation of the biologically inactive isoforms CCL14(1-74) and CCL14(11-74) is very inefficient. Thus, D6 cooperates with CD26 in the negative regulation of CCL14 by the selective degradation of its biologically active isoform. Analysis of a panel of CC chemokines and their truncated isoforms revealed that D6-mediated chemokine degradation does not correlate with binding affinity. Conversely, degradation efficiency is positively correlated with D6 adaptive up-regulation. Sequence analysis indicated that a proline residue in position 2 of D6 ligands is dispensable for binding but crucial for D6 adaptive up-regulation and efficient degradation.

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“…HCC-1 has been recently described as a human chemokine that is constitutively expressed in various tissues and is present at high concentrations in plasma. 39 However, the major source of circulating HCC-1 is unknown. High expression of HCC-1 in ATRA stimulated NB4 cells suggests that like CCL20, 40 the circulating HCC-1 might be produced by neutrophils.…”

Section: Regulation Of the Expression Of Cytokines And Chemokines By mentioning

confidence: 99%

Gene Expression Profiling during All-trans Retinoic Acid-Induced Cell Differentiation of Acute Promyelocytic Leukemia Cells

Yang

Zhao

et al. 2003

The Journal of Molecular Diagnostics

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Using cDNA microarrays we determined the gene expression patterns in the human acute promyelocytic leukemia (APL) cell line NB4 during all-trans retinoic acid (ATRA)-induced differentiation. We analyzed the expression of 12,288 genes in the NB4 cells after 12 hours, 24 hours, 48 hours, 72 hours, and 96 hours of ATRA exposure. During this time course, we found 168 up-regulated and more than 179 down-regulated genes, most of which have not been reported before. Many of the altered genes encode products that participate in signaling pathways, cell differentiation, programmed cell death, transcription regulation, and production of cytokines and chemokines. Of interest, the CD52 and protein kinase A regulatory subunit ␣ (PKA-Rl␣) genes, whose products are being used as therapeutic targets for certain human neoplasias in currently ongoing clinical trials, were among the genes observed to be markedly up-regulated after ATRA treatment. The present study provides valuable data to further understand the mechanism of ATRAinduced APL cell differentiation and suggests potential therapeutic alternatives for this leukemia. Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia characterized by the accumulation of cells arrested at the promyelocytic stage of myeloid differentiation. This leukemia exhibits a specific chromosomal translocation t(15;17) involving the promyelocytic leukemia (PML) gene locus on chromosome 15, and the retinoid acid receptor ␣ (RAR␣) locus on chromosome 17. This translocation generates a chimeric fusion gene PML-RAR␣, which encodes a protein that functions as an aberrant nuclear receptor considered to be the cause of APL.

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Urokinase Plasminogen Activator and Plasmin Efficiently Convert Hemofiltrate CC Chemokine 1 into Its Active [9–74] Processed Variant

Cited by 51 publications

References 64 publications

Proteolytic Activation of Alternative CCR1 Ligands in Inflammation

Proteolytic Activation of Alternative CCR1 Ligands in Inflammation

Recognition Versus Adaptive Up-regulation and Degradation of CC Chemokines by the Chemokine Decoy Receptor D6 Are Determined by Their N-terminal Sequence

Gene Expression Profiling during All-trans Retinoic Acid-Induced Cell Differentiation of Acute Promyelocytic Leukemia Cells

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