Abstract:
:Human monocytes isolated from peripheral blood of healthy donors show a time-dependent differentiation into macrophages upon in vitro cultivation, closely mimicking their in vivo migration and maturation into extravascular tissues. The mediator(s) of this maturation process has not been yet defined. We investigated the involvement of signal transducers and activators of transcription (STAT) factors in this phenomenon and reported the specific, time-dependent, activation of STAT1 protein starting at day 0/1 of cultivation and maximally expressed at day 5. STAT1 activity was evident on the STAT binding sequences (SBE) present in the promoters of genes which are up-regulated during monocyte to macrophage maturation such as FcgammaRI and ICAM-1, and in the promoter of the transcription factor IFN regulatory factor-1. Moreover, the effect of cell adhesion to fibronectin or laminin was studied to investigate mechanisms involved in STAT1 activation. Compared with monocytes adherent on plastic surfaces, freshly isolated cells allowed to adhere either to fibronectin- or laminin-coated flasks exhibited an increased STAT1 binding activity both in control and in IFN-gamma-treated cells. The molecular events leading to enhanced STAT1 activation and cytokine responsiveness concerned both Y701 and S727 STAT1 phosphorylation. Exogenous addition of transforming growth factor-beta, which exerts an inhibitory effect on some monocytic differentiation markers, inhibited macrophage maturation, integrin expression and STAT1 binding activity. Taken together these results indicate that STAT1 plays a pivotal role in the differentiation/maturation process of monocytes as an early transcription factor initially activated by adherence and then able to modulate the expression of functional genes, such as ICAM-1 and FcgammaRI.
journal_name
Int Immunoljournal_title
International immunologyauthors
Coccia EM,Del Russo N,Stellacci E,Testa U,Marziali G,Battistini Adoi
10.1093/intimm/11.7.1075subject
Has Abstractpub_date
1999-07-01 00:00:00pages
1075-83issue
7eissn
0953-8178issn
1460-2377journal_volume
11pub_type
杂志文章abstract::Mice lacking the IL-2 receptor beta chain (IL-2R beta) exhibit an autoimmune reaction characterized by generalized T cell activation, production of autoantibodies, myeloproliferation and severe anemia. T cells of IL-2R beta-/- mice were examined to elucidate the mechanism responsible for their abnormal activation and ...
journal_title:International immunology
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journal_title:International immunology
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abstract::The functional maturation process of medullary-type CD4(-)CD8(+) [CD8 single-positive (SP)] thymocytes remains largely uncharacterized. We describe a phenotypic analysis of CD8 SP medullary-type thymocytes and find a remarkable heterogeneity within this thymic cell population. While mature CD8(+) T cells in the periph...
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doi:10.1093/intimm/13.3.313
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journal_title:International immunology
pub_type: 杂志文章,评审
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更新日期:2016-01-01 00:00:00
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journal_title:International immunology
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更新日期:2001-10-01 00:00:00
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journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxn038
更新日期:2008-07-01 00:00:00
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journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxq434
更新日期:2010-10-01 00:00:00
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doi:10.1093/intimm/dxp053
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doi:10.1093/intimm/dxu105
更新日期:2015-05-01 00:00:00
abstract::Invariant natural killer T (iNKT) cells expressing the retinoic acid receptor-related orphan receptor γt (RORγt) and producing IL-17 represent a minor subset of CD1d-restricted iNKT cells (iNKT17) in C57BL/6J (B6) mice. We aimed in this study to define the reasons for their low distribution and the sequence of events ...
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doi:10.1093/intimm/dxz064
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doi:10.1093/intimm/7.4.541
更新日期:1995-04-01 00:00:00
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pub_type: 杂志文章
doi:10.1093/intimm/12.11.1511
更新日期:2000-11-01 00:00:00
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journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxh064
更新日期:2004-04-01 00:00:00
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journal_title:International immunology
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更新日期:1994-03-01 00:00:00
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pub_type: 杂志文章
doi:10.1093/intimm/7.3.369
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pub_type: 杂志文章
doi:10.1093/intimm/1.5.503
更新日期:1989-01-01 00:00:00
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journal_title:International immunology
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更新日期:2006-08-01 00:00:00
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journal_title:International immunology
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更新日期:2008-06-01 00:00:00