| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Laboratory of Molecular Biology, G. Gaslini Institute, and
Functional Genomics, National Cancer Research Institute, Genova, Italy; and
University of Insubria, Varese, Italy
Peripheral blood monocytes migrate to and accumulate in hypoxic areas of inflammatory and tumor lesions. To characterize the molecular bases underlying monocyte functions within a hypoxic microenvironment, we investigated the transcriptional profile induced by hypoxia in primary human monocytes using high-density oligonucleotide microarrays. Profound changes in the gene expression pattern were detected following 16 h exposure to 1% O2, with 536 and 677 sequences showing at least a 1.5-fold increase and decrease, respectively. Validation of this analysis was provided by quantitative RT-PCR confirmation of expression differences of selected genes. Among modulated genes, 74 were known hypoxia-responsive genes, whereas the majority were new genes whose responsiveness to hypoxia had not been previously described. The hypoxic transcriptome was characterized by the modulation of a significant cluster of genes with immunological relevance. These included scavenger receptors (CD163, STAB1, C1qR1, MSR1, MARCO, TLR7), immunoregulatory, costimulatory, and adhesion molecules (CD32, CD64, CD69, CD89, CMRF-35H, ITGB5, LAIR1, LIR9), chemokines/cytokines and receptors (CCL23, CCL15, CCL8, CCR1, CCR2, RDC1, IL-23A, IL-6ST). Furthermore, we provided conclusive evidence of hypoxic induction of CCL20, a chemoattractant for immature dendritic cells, activated/memory T lymphocytes, and naive B cells. CCL20 mRNA up-regulation was paralleled by increased protein expression and secretion. This study represents the first transcriptome analysis of hypoxic primary human monocytes, which provides novel insights into monocyte functional behavior within ischemic/hypoxic tissues. CCL20 up-regulation by hypoxia may constitute an important mechanism to promote recruitment of specific leukocyte subsets at pathological sites and may have implications for the pathogenesis of chronic inflammatory diseases.
This article has been cited by other articles:
|
|
 |
|
  R. Cheung, M. Malik, V. Ravyn, B. Tomkowicz, A. Ptasznik, and R. G. Collman An arrestin-dependent multi-kinase signaling complex mediates MIP-1{beta}/CCL4 signaling and chemotaxis of primary human macrophages J. Leukoc. Biol., October 1, 2009; 86(4): 833 - 845. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-o Deguchi, H. Yamazaki, E. Aikawa, and M. Aikawa Chronic Hypoxia Activates the Akt and {beta}-Catenin Pathways in Human Macrophages Arterioscler Thromb Vasc Biol, October 1, 2009; 29(10): 1664 - 1670. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Carmi, E. Voronov, S. Dotan, N. Lahat, M. A. Rahat, M. Fogel, M. Huszar, M. R. White, C. A. Dinarello, and R. N. Apte The Role of Macrophage-Derived IL-1 in Induction and Maintenance of Angiogenesis J. Immunol., October 1, 2009; 183(7): 4705 - 4714. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-Y. Fang, R. Hughes, C. Murdoch, S. B. Coffelt, S. K. Biswas, A. L. Harris, R. S. Johnson, H. Z. Imityaz, M. C. Simon, E. Fredlund, et al. Hypoxia-inducible factors 1 and 2 are important transcriptional effectors in primary macrophages experiencing hypoxia Blood, July 23, 2009; 114(4): 844 - 859. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. BOSCO, S. DELFINO, F. FERLITO, M. PUPPO, A. GREGORIO, C. GAMBINI, M. GATTORNO, A. MARTINI, and L. VARESIO The Hypoxic Synovial Environment Regulates Expression of Vascular Endothelial Growth Factor and Osteopontin in Juvenile Idiopathic Arthritis J Rheumatol, June 1, 2009; 36(6): 1318 - 1329. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. Elia, P. Cappello, M. Puppo, T. Fraone, C. Vanni, A. Eva, T. Musso, F. Novelli, L. Varesio, and M. Giovarelli Human dendritic cells differentiated in hypoxia down-modulate antigen uptake and change their chemokine expression profile J. Leukoc. Biol., December 1, 2008; 84(6): 1472 - 1482. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Puppo, F. Battaglia, C. Ottaviano, S. Delfino, D. Ribatti, L. Varesio, and M. C. Bosco Topotecan inhibits vascular endothelial growth factor production and angiogenic activity induced by hypoxia in human neuroblastoma by targeting hypoxia-inducible factor-1{alpha} and -2{alpha} Mol. Cancer Ther., July 1, 2008; 7(7): 1974 - 1984. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 B. Brune and J. Zhou Nitric oxide and superoxide: Interference with hypoxic signaling Cardiovasc Res, July 15, 2007; 75(2): 275 - 282. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Proost, A. Mortier, T. Loos, J. Vandercappellen, M. Gouwy, I. Ronsse, E. Schutyser, W. Put, M. Parmentier, S. Struyf, et al. Proteolytic processing of CXCL11 by CD13/aminopeptidase N impairs CXCR3 and CXCR7 binding and signaling and reduces lymphocyte and endothelial cell migration Blood, July 1, 2007; 110(1): 37 - 44. [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]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
