PMID- 17641060
OWN - NLM
STAT- MEDLINE
DCOM- 20070917
LR  - 20190516
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 179
IP  - 3
DP  - 2007 Aug 1
TI  - Identification of Pur alpha as a new hypoxia response factor responsible for 
      coordinated induction of the beta 2 integrin family.
PG  - 1934-41
AB  - Central to the process of inflammation are hypoxic conditions that lead to the 
      binding of circulating leukocytes to the endothelium. We have previously shown 
      that such binding is mediated by monocytes being able to directly sense hypoxic 
      conditions and respond by inducing their surface expression of the beta(2) 
      integrin family of adhesion molecules. In this study, we show that coordinated 
      induction of the beta(2) integrins during direct hypoxia-sensing occurs through 
      transcriptional activation of each of the genes by which they are encoded. 
      Certain of the molecular mechanisms that mediate this activation in transcription 
      are dependent upon hypoxia-inducible factor-1 (HIF-1), whereas others are HIF-1 
      independent. In search of these HIF-1-independent mechanisms, we identified Pur 
      alpha as a new hypoxia-response factor. Binding of Pur alpha to the 
      HIF-1-independent beta(2) integrin promoters is induced by hypoxia and 
      mutagenesis of these Pur alpha-binding sites almost completely abolishes the 
      ability of the promoters to respond to hypoxic conditions. Additional studies 
      using siRNA directed against Pur alpha also revealed a loss in the hypoxic 
      response of the beta(2) integrin promoters. Taken together, our findings 
      demonstrate that hypoxia induces a coordinated up-regulation in beta(2) integrin 
      expression that is dependent upon transcriptional mechanisms mediated by HIF-1 
      and Pur alpha.
FAU - Kong, Tianqing
AU  - Kong T
AD  - Renal Division, Department of Medicine, Brigham and Women's Hospital, and Harvard 
      Medical School, Boston, MA 02115, USA.
FAU - Scully, Melanie
AU  - Scully M
FAU - Shelley, C Simon
AU  - Shelley CS
FAU - Colgan, Sean P
AU  - Colgan SP
LA  - eng
GR  - DE016191/DE/NIDCR NIH HHS/United States
GR  - DK50189/DK/NIDDK NIH HHS/United States
GR  - HL60569/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (CD11 Antigens)
RN  - 0 (CD11b Antigen)
RN  - 0 (CD11c Antigen)
RN  - 0 (CD18 Antigens)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Membrane Proteins)
RN  - 0 (PURA protein, human)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - CD11 Antigens/biosynthesis/genetics
MH  - CD11b Antigen/biosynthesis/genetics
MH  - CD11c Antigen/biosynthesis/genetics
MH  - CD18 Antigens/*biosynthesis/*genetics/metabolism
MH  - Cell Adhesion/genetics/immunology
MH  - Cells, Cultured
MH  - DNA-Binding Proteins/biosynthesis/genetics/metabolism/*physiology
MH  - Endothelium, Vascular/immunology/metabolism/pathology
MH  - Humans
MH  - Hypoxia/genetics/immunology/*metabolism
MH  - Hypoxia-Inducible Factor 1/*physiology
MH  - Leukocytes/immunology/metabolism/pathology
MH  - Membrane Proteins/biosynthesis/genetics
MH  - Multigene Family
MH  - Promoter Regions, Genetic
MH  - Protein Binding/genetics/immunology
MH  - RNA, Messenger/biosynthesis
MH  - Transcription Factors/biosynthesis/genetics/metabolism/*physiology
MH  - U937 Cells
MH  - Up-Regulation/genetics/immunology
EDAT- 2007/07/21 09:00
MHDA- 2007/09/18 09:00
CRDT- 2007/07/21 09:00
PHST- 2007/07/21 09:00 [pubmed]
PHST- 2007/09/18 09:00 [medline]
PHST- 2007/07/21 09:00 [entrez]
AID - 179/3/1934 [pii]
AID - 10.4049/jimmunol.179.3.1934 [doi]
PST - ppublish
SO  - J Immunol. 2007 Aug 1;179(3):1934-41. doi: 10.4049/jimmunol.179.3.1934.