Chapter title |
Macrophage activating properties of the tryptophan catabolite picolinic acid.
|
---|---|
Chapter number | 6 |
Book title |
Developments in Tryptophan and Serotonin Metabolism
|
Published in |
Advances in experimental medicine and biology, June 2004
|
DOI | 10.1007/978-1-4615-0135-0_6 |
Pubmed ID | |
Book ISBNs |
978-1-4613-4939-6, 978-1-4615-0135-0
|
Authors |
Bosco MC, Rapisarda A, Reffo G, Massazza S, Pastorino S, Varesio L, Maria Carla Bosco, Annamaria Rapisarda, Gioia Reffo, Stefano Massazza, Sandra Pastorino, Luigi Varesio, Bosco, Maria Carla, Rapisarda, Annamaria, Reffo, Gioia, Massazza, Stefano, Pastorino, Sandra, Varesio, Luigi |
Abstract |
Recent studies have suggested a role for aminoacid catabolites as important regulators of macrophage (Mphi) activities. We reported previously that picolinic acid (PA), a tryptophan catabolite produced under inflammatory conditions and a costimulus with IFNgamma of Mphi effector functions, is a selective inducer of the Mphi inflammatory protein-1alpha (MIP-1alpha) and -1beta (MIPs), two CC-chemokines involved in the elicitation of the inflammatory reactions and in the development of the Th1 responses. In this study, we have investigated the effects of IFNgamma on PA-induced MIPs expression and secretion by mouse Mphi as well as the regulation of MIP-1alpha/beta receptor, CCR5, by both stimuli alone or in combination. We demonstrated that IFNgamma inhibited MIPs mRNA stimulation by PA in a dose-and time-dependent fashion, despite its ability to induce other CC- or CXC chemokines. MIPs mRNA down-regulation was associated with decreased intracellular chemokine expression and secretion and was dependent on both mRNA destabilization and gene transcription inhibition. Moreover, IFNgamma inhibitory effects were stimulus-specific because MIPs induction by PA was either unaffected or increased by the anti-inflammatory cytokines, IL-10 and IL-4, or the pro-inflammatory stimulus, LPS, respectively. In contrast, we found that IFNgamma increased CCR5 basal expression, whereas PA down-regulated both constitutive and IFNgamma-induced CCR5 mRNA and protein levels. These results demonstrate that IFNgamma and PA have reciprocal effects on the production of MIPs chemokines and the expression of their receptor. The concerted action of IFNgamma and PA on MIP-1alpha/beta chemokine/receptor system is likely to be of pathophysiological significance and to represent an important regulatory mechanism for leukocyte recruitment and distribution into damaged tissues during inflammatory responses. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 1 | 4% |
Unknown | 22 | 96% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 4 | 17% |
Student > Ph. D. Student | 4 | 17% |
Student > Bachelor | 3 | 13% |
Student > Master | 2 | 9% |
Librarian | 1 | 4% |
Other | 3 | 13% |
Unknown | 6 | 26% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 4 | 17% |
Agricultural and Biological Sciences | 3 | 13% |
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 9% |
Biochemistry, Genetics and Molecular Biology | 2 | 9% |
Nursing and Health Professions | 1 | 4% |
Other | 1 | 4% |
Unknown | 10 | 43% |