The undecided serpin

Medcalf, Robert L.; Stasinopoulos, Stan

doi:10.1111/j.1742-4658.2005.04879.x

Cited by 117 publications

(39 citation statements)

References 89 publications

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“…Binding of gp120 to CD4 also rapidly induces TNF␣ (28) and IL-1 secretion (51), inflammatory mediators known to induce SerpinB2 (2). Stabilization of SerpinB2 mRNA may also be involved (2). The reduction in SerpinB2 expression apparent by day 10 after infection ( Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Under certain conditions HIV-1 replication in vivo is likely to occur in monocytes/macrophages expressing SerpinB2. Certain inflammatory conditions (22), TNF␣ (23) and bacterial infections (21,24) enhance the replication of HIV-1 in monocytes/ macrophages and potently induce SerpinB2 expression in these cells (2). These considerations and the reported influence of SerpinB2 expression on transcription (15,16,19), prompted an investigation of the role of SerpinB2 expression in HIV-1 infection.…”

mentioning

confidence: 99%

“…SerpinB2, also known as plasminogen activator inhibitor type-2 (PAI-2), 2 is one of the most abundant proteins of activated monocytes and macrophages, whose expression is substantially up-regulated during most inflammatory processes (1,2). SerpinB2 is also induced following infection with a range of parasitic (3,4), viral (5)(6)(7)(8), and bacterial (9 -12) pathogens.…”

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confidence: 99%

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SerpinB2 Is an Inducible Host Factor Involved in Enhancing HIV-1 Transcription and Replication

Darnell¹,

Schroder²,

Gardner³

et al. 2006

J. Biol. Chem.

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The serine protease inhibitor SerpinB2 (plasminogen activator inhibitor-2) is a major product of activated monocytes and macrophages and is substantially induced during most inflammatory processes. Distinct from its widely described extracellular role as an inhibitor of urokinase plasminogen activator, SerpinB2 has recently been shown to have an intracellular role as a retinoblastoma protein (Rb)-binding protein that inhibits Rb degradation. Here we show that HIV-1 infection and gp120 treatment of human peripheral blood mononuclear cells resulted in induction of SerpinB2. Furthermore, SerpinB2 expression in THP-1 monocyte/macrophage, Jurkat T, and HeLa cell lines increased replication of HIV-1 and enhanced transcription from the HIV-1 long terminal repeat (LTR) promoter by 3-10-fold. Increased HIV-1 gene expression and transcription was also observed in activated macrophages from SerpinB2 ؉/؉ mice compared with macrophages from SerpinB2 ؊/؊ mice. The SerpinB2-mediated elevation of Rb protein levels appeared to be responsible for enhancing transcription from the core promoter region of the LTR by relieving HDM2-mediated inhibition of Sp1 and/or by increasing the Sp1/Sp3 expression ratios. This is the first report associating HIV-1 replication with SerpinB2 expression and illustrates that SerpinB2 is a potentially important inducible host factor that significantly promotes HIV-1 replication.SerpinB2, also known as plasminogen activator inhibitor type-2 (PAI-2), 2 is one of the most abundant proteins of activated monocytes and macrophages, whose expression is substantially up-regulated during most inflammatory processes (1, 2). SerpinB2 is also induced following infection with a range of parasitic (3, 4), viral (5-8), and bacterial (9 -12) pathogens. Although SerpinB2 is widely described as an inhibitor of the extracellular urokinase plasminogen activator, the evidence that SerpinB2 has a major physiological role in the regulation of plasminogen activation is not compelling (13). SerpinB2 is a member of the Clade B or ovalbumin-like serine protease inhibitor (ov-serpin) subgroup of serpins, which lack a classical secretory signal peptide and are frequently found to reside intracellularly with a cytoplasmic or nucleocytoplasmic distribution (14). SerpinB2 has recently been shown to have an intranuclear activity as a retinoblastoma protein (Rb)-binding protein (15-18). SerpinB2 expression inhibited Rb degradation, which resulted in increased Rb protein levels. This activity required both (i) the C-D interhelical region of SerpinB2, which mediates Rb binding, and (ii) the reactive site loop (RSL), which mediates the protease inhibitory activity of SerpinB2. The SerpinB2-mediated increase in Rb protein levels was found to enhance Rb-mediated activities, such as repression of E2F-1-dependent gene expression and promotion of G 1 cell cycle arrest (15). SerpinB2 expression has also been shown to influence transcription of mammalian (15, 19) and viral genes (16), with the latter two studies illustrating that this activity ...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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SerpinB2 Is an Inducible Host Factor Involved in Enhancing HIV-1 Transcription and Replication

Darnell¹,

Schroder²,

Gardner³

et al. 2006

J. Biol. Chem.

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“…In addition to its function in blood coagulation, SERPINB2 plays roles in cell proliferation, apoptosis inhibition and inflammation [23,24]. ANGPTL6 promotes the formation of new blood vessels, wound healing process and is thought to regulate energy metabolism [25][26][27].…”

Section: Genes Related To Hemostasis and Angiogenesismentioning

confidence: 99%

Characterization of frataxin gene network in Friedreich's ataxia fibroblasts using the RNA-Seq technique

et al. 2016

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“…SerpinB2 [also known as plasminogen activator inhibitor-2 (PAI-2)] is a serine protease inhibitor, which exists largely as a 47-kDa intracellular form and may also be secreted as a 60-kDa glycosylated protein (25). Like plasminogen activator inhibitor-1 (PAI-1), SerpinB2 inhibits tissue-type and urokinase-type plasminogen activators (tPA and uPA), prevents activation of plasmin, and promotes fibrin formation.…”

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confidence: 99%

Genome-wide profiling identifies epithelial cell genes associated with asthma and with treatment response to corticosteroids

Woodruff

Boushey

Dolganov

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

759

677

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Airway inflammation and epithelial remodeling are two key features of asthma. IL-13 and other cytokines produced during T helper type 2 cell-driven allergic inflammation contribute to airway epithelial goblet cell metaplasia and may alter epithelial-mesenchymal signaling, leading to increased subepithelial fibrosis or hyperplasia of smooth muscle. The beneficial effects of corticosteroids in asthma could relate to their ability to directly or indirectly decrease epithelial cell activation by inflammatory cells and cytokines. To identify markers of epithelial cell dysfunction and the effects of corticosteroids on epithelial cells in asthma, we studied airway epithelial cells collected from asthmatic subjects enrolled in a randomized controlled trial of inhaled corticosteroids, from healthy subjects and from smokers (disease control). By using gene expression microarrays, we found that chloride channel, calciumactivated, family member 1 (CLCA1), periostin, and serine peptidase inhibitor, clade B (ovalbumin), member 2 (serpinB2) were up-regulated in asthma but not in smokers. Corticosteroid treatment down-regulated expression of these three genes and markedly up-regulated expression of FK506-binding protein 51 (FKBP51). Whereas high baseline expression of CLCA1, periostin, and serpinB2 was associated with a good clinical response to corticosteroids, high expression of FKBP51 was associated with a poor response. By using airway epithelial cells in culture, we found that IL-13 increased expression of CLCA1, periostin, and serpinB2, an effect that was suppressed by corticosteroids. Corticosteroids also induced expression of FKBP51. Taken together, our findings show that airway epithelial cells in asthma have a distinct activation profile and identify direct and cell-autonomous effects of corticosteroid treatment on airway epithelial cells that relate to treatment responses and can now be the focus of specific mechanistic studies.gene expression microarray ͉ serpinB2 ͉ CLCA1 ͉ FKBP51

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The undecided serpin

Cited by 117 publications

References 89 publications

SerpinB2 Is an Inducible Host Factor Involved in Enhancing HIV-1 Transcription and Replication

SerpinB2 Is an Inducible Host Factor Involved in Enhancing HIV-1 Transcription and Replication

Characterization of frataxin gene network in Friedreich's ataxia fibroblasts using the RNA-Seq technique

Genome-wide profiling identifies epithelial cell genes associated with asthma and with treatment response to corticosteroids

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