| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
and -1ß in Macrophages1
*
Laboratory of Molecular Biology, G. Gaslini Institute, Genova, Italy;
DTP-Tumor Hypoxia Program and
Laboratory of Experimental Immunology, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702
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)-1
and MIP-1ß (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-
-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- did not affect MIPs expression. Induction of
both MIP-1 and MIP-1ß 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.
This article has been cited by other articles:
|
|
 |
|
  F. Battaglia, S. Delfino, E. Merello, M. Puppo, R. Piva, L. Varesio, and M. C. Bosco Hypoxia transcriptionally induces macrophage-inflammatory protein-3{alpha}/CCL-20 in primary human mononuclear phagocytes through nuclear factor (NF)-{kappa}B J. Leukoc. Biol., March 1, 2008; 83(3): 648 - 662. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Ricciardi, A. R. Elia, P. Cappello, M. Puppo, C. Vanni, P. Fardin, A. Eva, D. Munroe, X. Wu, M. Giovarelli, et al. Transcriptome of Hypoxic Immature Dendritic Cells: Modulation of Chemokine/Receptor Expression Mol. Cancer Res., February 1, 2008; 6(2): 175 - 185. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. J. Guillemin, K. M. Cullen, C. K. Lim, G. A. Smythe, B. Garner, V. Kapoor, O. Takikawa, and B. J. Brew Characterization of the Kynurenine Pathway in Human Neurons J. Neurosci., November 21, 2007; 27(47): 12884 - 12892. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Puppo, M. C. Bosco, M. Federico, S. Pastorino, and L. Varesio Hypoxia inhibits Moloney murine leukemia virus expression in activated macrophages J. Leukoc. Biol., February 1, 2007; 81(2): 528 - 538. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Bosco, M. Puppo, C. Santangelo, L. Anfosso, U. Pfeffer, P. Fardin, F. Battaglia, and L. Varesio Hypoxia Modifies the Transcriptome of Primary Human Monocytes: Modulation of Novel Immune-Related Genes and Identification Of CC-Chemokine Ligand 20 as a New Hypoxia-Inducible Gene J. Immunol., August 1, 2006; 177(3): 1941 - 1955. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Clark, G. M. Mackay, G. A. Smythe, S. Bustamante, T. W. Stone, and R. S. Phillips Prolonged Survival of a Murine Model of Cerebral Malaria by Kynurenine Pathway Inhibition Infect. Immun., August 1, 2005; 73(8): 5249 - 5251. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Bosco, M. Puppo, S. Pastorino, Z. Mi, G. Melillo, S. Massazza, A. Rapisarda, and L. Varesio Hypoxia Selectively Inhibits Monocyte Chemoattractant Protein-1 Production by Macrophages J. Immunol., February 1, 2004; 172(3): 1681 - 1690. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Tanabe, Y. Egashira, S.-I. Fukuoka, K. Shibata, and H. Sanada Expression of Rat Hepatic 2-Amino-3-Carboxymuconate-6-Semialdehyde Decarboxylase Is Affected by a High Protein Diet and by Streptozotocin-Induced Diabetes J. Nutr., June 1, 2002; 132(6): 1153 - 1159. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
