The tryptophan catabolite picolinic acid selectively induces the chemokines macrophage inflammatory protein-1α and -1β in macrophages

Maria Carla Bosco, Annamaria Rapisarda, Stefano Massazza, Giovanni Melillo, Howard Young, Luigi Varesio

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

We previously found that the tryptophan catabolite picolinic acid (PA) is a costimulus for the activation of macrophage effector functions. In this study, we have investigated the ability of PA to modulate the expression of chemokines in macrophages. We demonstrate that PA is a potent activator of the inflammatory chemokines MIP (macrophage inflammatory protein)-1α and MIP-1β (MIPs) mRNA expression in mouse macrophages in a dose- and time- dependent fashion and through a de novo protein synthesis-dependent process. The induction by PA occurred within 3 h of treatment and reached a peak in 12 h. The stimulatory effects of PA were selective for MIPs because other chemokines, including monocyte chemoattractant protein-1, RANTES, IFN-γ- inducible protein-10, MIP-2, and macrophage-derived chemokine, were not induced under the same experimental conditions and were not an epiphenomenon of macrophage activation because IFN-γ did not affect MIPs expression. Induction of both MIP-1α and MIP-1β by PA was associated with transcriptional activation and mRNA stabilization, suggesting a dual molecular mechanism of control. Iron chelation could be involved in MIPs induction by PA because iron sulfate inhibited the process and the iron- chelating agent, desferrioxamine, induced MIPs expression. We propose the existence of a new pathway leading to inflammation initiated by tryptophan catabolism that can communicate with the immune system through the production of PA, followed by secretion of chemokines by macrophages. These results establish the importance of PA as an activator of macrophage proinflammatory functions, providing the first evidence that this molecule can be biologically active without the need for a costimulatory agent.

Original languageEnglish
Pages (from-to)3283-3291
Number of pages9
JournalJournal of Immunology
Volume164
Issue number6
Publication statusPublished - Mar 15 2000

Fingerprint

Macrophage Inflammatory Proteins
Chemokines
Tryptophan
Macrophages
Macrophage Activation
Chemokine CCL22
Iron
Iron Chelating Agents
Chemokine CXCL2
picolinic acid
Chemokine CCL5
Messenger RNA
Deferoxamine
Chemokine CCL2
Transcriptional Activation
Sulfates
Immune System
Proteins
Inflammation

ASJC Scopus subject areas

  • Immunology

Cite this

The tryptophan catabolite picolinic acid selectively induces the chemokines macrophage inflammatory protein-1α and -1β in macrophages. / Bosco, Maria Carla; Rapisarda, Annamaria; Massazza, Stefano; Melillo, Giovanni; Young, Howard; Varesio, Luigi.

In: Journal of Immunology, Vol. 164, No. 6, 15.03.2000, p. 3283-3291.

Research output: Contribution to journalArticle

Bosco, Maria Carla ; Rapisarda, Annamaria ; Massazza, Stefano ; Melillo, Giovanni ; Young, Howard ; Varesio, Luigi. / The tryptophan catabolite picolinic acid selectively induces the chemokines macrophage inflammatory protein-1α and -1β in macrophages. In: Journal of Immunology. 2000 ; Vol. 164, No. 6. pp. 3283-3291.
@article{ee46e58b0a58476bbb224e406539a408,
title = "The tryptophan catabolite picolinic acid selectively induces the chemokines macrophage inflammatory protein-1α and -1β in macrophages",
abstract = "We previously found that the tryptophan catabolite picolinic acid (PA) is a costimulus for the activation of macrophage effector functions. In this study, we have investigated the ability of PA to modulate the expression of chemokines in macrophages. We demonstrate that PA is a potent activator of the inflammatory chemokines MIP (macrophage inflammatory protein)-1α and MIP-1β (MIPs) mRNA expression in mouse macrophages in a dose- and time- dependent fashion and through a de novo protein synthesis-dependent process. The induction by PA occurred within 3 h of treatment and reached a peak in 12 h. The stimulatory effects of PA were selective for MIPs because other chemokines, including monocyte chemoattractant protein-1, RANTES, IFN-γ- inducible protein-10, MIP-2, and macrophage-derived chemokine, were not induced under the same experimental conditions and were not an epiphenomenon of macrophage activation because IFN-γ did not affect MIPs expression. Induction of both MIP-1α and MIP-1β by PA was associated with transcriptional activation and mRNA stabilization, suggesting a dual molecular mechanism of control. Iron chelation could be involved in MIPs induction by PA because iron sulfate inhibited the process and the iron- chelating agent, desferrioxamine, induced MIPs expression. We propose the existence of a new pathway leading to inflammation initiated by tryptophan catabolism that can communicate with the immune system through the production of PA, followed by secretion of chemokines by macrophages. These results establish the importance of PA as an activator of macrophage proinflammatory functions, providing the first evidence that this molecule can be biologically active without the need for a costimulatory agent.",
author = "Bosco, {Maria Carla} and Annamaria Rapisarda and Stefano Massazza and Giovanni Melillo and Howard Young and Luigi Varesio",
year = "2000",
month = "3",
day = "15",
language = "English",
volume = "164",
pages = "3283--3291",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "6",

}

TY - JOUR

T1 - The tryptophan catabolite picolinic acid selectively induces the chemokines macrophage inflammatory protein-1α and -1β in macrophages

AU - Bosco, Maria Carla

AU - Rapisarda, Annamaria

AU - Massazza, Stefano

AU - Melillo, Giovanni

AU - Young, Howard

AU - Varesio, Luigi

PY - 2000/3/15

Y1 - 2000/3/15

N2 - We previously found that the tryptophan catabolite picolinic acid (PA) is a costimulus for the activation of macrophage effector functions. In this study, we have investigated the ability of PA to modulate the expression of chemokines in macrophages. We demonstrate that PA is a potent activator of the inflammatory chemokines MIP (macrophage inflammatory protein)-1α and MIP-1β (MIPs) mRNA expression in mouse macrophages in a dose- and time- dependent fashion and through a de novo protein synthesis-dependent process. The induction by PA occurred within 3 h of treatment and reached a peak in 12 h. The stimulatory effects of PA were selective for MIPs because other chemokines, including monocyte chemoattractant protein-1, RANTES, IFN-γ- inducible protein-10, MIP-2, and macrophage-derived chemokine, were not induced under the same experimental conditions and were not an epiphenomenon of macrophage activation because IFN-γ did not affect MIPs expression. Induction of both MIP-1α and MIP-1β by PA was associated with transcriptional activation and mRNA stabilization, suggesting a dual molecular mechanism of control. Iron chelation could be involved in MIPs induction by PA because iron sulfate inhibited the process and the iron- chelating agent, desferrioxamine, induced MIPs expression. We propose the existence of a new pathway leading to inflammation initiated by tryptophan catabolism that can communicate with the immune system through the production of PA, followed by secretion of chemokines by macrophages. These results establish the importance of PA as an activator of macrophage proinflammatory functions, providing the first evidence that this molecule can be biologically active without the need for a costimulatory agent.

AB - We previously found that the tryptophan catabolite picolinic acid (PA) is a costimulus for the activation of macrophage effector functions. In this study, we have investigated the ability of PA to modulate the expression of chemokines in macrophages. We demonstrate that PA is a potent activator of the inflammatory chemokines MIP (macrophage inflammatory protein)-1α and MIP-1β (MIPs) mRNA expression in mouse macrophages in a dose- and time- dependent fashion and through a de novo protein synthesis-dependent process. The induction by PA occurred within 3 h of treatment and reached a peak in 12 h. The stimulatory effects of PA were selective for MIPs because other chemokines, including monocyte chemoattractant protein-1, RANTES, IFN-γ- inducible protein-10, MIP-2, and macrophage-derived chemokine, were not induced under the same experimental conditions and were not an epiphenomenon of macrophage activation because IFN-γ did not affect MIPs expression. Induction of both MIP-1α and MIP-1β by PA was associated with transcriptional activation and mRNA stabilization, suggesting a dual molecular mechanism of control. Iron chelation could be involved in MIPs induction by PA because iron sulfate inhibited the process and the iron- chelating agent, desferrioxamine, induced MIPs expression. We propose the existence of a new pathway leading to inflammation initiated by tryptophan catabolism that can communicate with the immune system through the production of PA, followed by secretion of chemokines by macrophages. These results establish the importance of PA as an activator of macrophage proinflammatory functions, providing the first evidence that this molecule can be biologically active without the need for a costimulatory agent.

UR - http://www.scopus.com/inward/record.url?scp=0034653396&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034653396&partnerID=8YFLogxK

M3 - Article

C2 - 10706721

AN - SCOPUS:0034653396

VL - 164

SP - 3283

EP - 3291

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 6

ER -