16K prolactin induces NF-kappaB activation in pulmonary fibroblasts

Macotela, Yazmín; Mendoza, Criselda; Corbacho, Ana; Cosı́o, Gabriela; Eiserich, JP; Zentella, Alejandro; Escalera, Gonzálo Martínez de la; Clapp, Carmen

doi:10.1677/joe.0.175r013

Cited by 25 publications

(21 citation statements)

References 15 publications

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“…2). This is in contrast to the studies by Macotela et al (50) and Tabruyn et al (51), which showed that 16-kDa PRL activates NF-nB activity in primary mouse embryonic lung fibroblasts and bovine brain capillary endothelial cells, respectively. Because the IL-1h-inducible NF-nB pathway is essentially unperturbed by 16-kDa PRL in RAEC, these results may explain why 16-kDa PRL only inhibited f40% iNOS gene transcription, which is likely contributed by the IL-1h-inducible IRF-1 pathway.…”

Section: Discussioncontrasting

confidence: 99%

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16-kDa Prolactin Down-Regulates Inducible Nitric Oxide Synthase Expression through Inhibition of the Signal Transducer and Activator of Transcription 1/IFN Regulatory Factor-1 Pathway

Lee¹,

Nishino

Mazumdar³

et al. 2005

Cancer Research

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Angiogenesis plays a key role in promoting tumorigenesis and metastasis. Several antiangiogenic factors have been shown to inhibit tumor growth in animal models. Understanding their mechanism of action would allow for better therapeutic application. 16-kDa prolactin (PRL), a NH 2 -terminal natural breakdown fragment of the intact 23-kDa PRL, exerts potent antiangiogenic and antitumor activities. The signaling mechanism involved in 16-kDa PRL action in endothelial cells remains unclear. One of the actions of 16-kDa PRL is to attenuate the production of nitric oxide (NO) through the inhibition of inducible NO synthase (iNOS) expression in endothelial cells. To delineate the signaling mechanism from 16-kDa PRL, we examined the effect of 16-kDa PRL on interleukin IL-1B-inducible iNOS expression, which is regulated by two parallel pathways, one involving IFN regulatory factor 1 (IRF-1) and the other nuclear factor-KB (NF-KB). Our studies showed that 16-kDa PRL specifically blocked IRF-1 but not NF-KB signaling to the iNOS promoter. We found that IL-1B regulated IRF-1 gene expression through stimulation of p38 mitogen-activated protein kinase (MAPK), which mediated signal transducer and activator of transcription 1 (Stat1) serine phosphorylation and Stat1 nuclear translocation to activate the IRF-1 promoter. 16-kDa PRL effectively inhibited IL-1B-inducible p38 MAPK phosphorylation, resulting in blocking Stat1 serine phosphorylation, its subsequent nuclear translocation and activation of the Stat1 target gene IRF-1. Thus, 16-kDa PRL inhibits the p38 MAPK/Stat1/IRF-1 pathway to attenuate iNOS/NO production in endothelial cells. (Cancer Res 2005; 65(17): 7984-92)

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Section: Discussioncontrasting

confidence: 99%

“…3), Ras, Raf, ERK1/2 MAPK (12, 52), p38 MAPK (Fig. 5), and NF-nB (50,51), in a cell type-and tissue-specific manner.…”

Section: Discussionmentioning

confidence: 93%

16-kDa Prolactin Down-Regulates Inducible Nitric Oxide Synthase Expression through Inhibition of the Signal Transducer and Activator of Transcription 1/IFN Regulatory Factor-1 Pathway

Lee¹,

Nishino

Mazumdar³

et al. 2005

Cancer Research

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“…Prolactin receptor has recently been reported to be upregulated in the lungs of mice exposed to lipopolysaccharide, 53 and prolactin can activate the inflammatory natural killer (NF)-kb cascade in pulmonary fibroblasts. 54 It is therefore plausible that prolactin may play a role in the inflammatory environment in COPD.…”

Section: Discussionmentioning

confidence: 99%

Profiling serum biomarkers in patients with COPD: associations with clinical parameters

Pinto-Plata

Toso

Lee

et al. 2007

Thorax

172

164

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Background: Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease associated with significant systemic consequences. Recognition of the systemic manifestations has stimulated interest in identifying circulating biomarkers in these patients. A systematic analysis was undertaken of multiple protein analytes in the serum of well characterised patients with COPD and matched controls using novel protein microarray platform (PMP) technology. Methods: Forty-eight patients (65% men) with COPD (forced expiratory volume in 1 s ,55%) and 48 matched controls were studied. Anthropometric parameters, pulmonary function tests, 6-minute walk distance, the BODE index and the number of exacerbations were measured and the association of these outcomes with the baseline levels of 143 serum biomarkers measured by PMP was explored. Results: Thirty biomarker clusters were identified and ranked by computing the predictive value of each cluster for COPD (partial least squares discriminant analysis). From the 19 best predictive clusters, 2-3 biomarkers were selected based on their pathophysiological profile (chemoattractants, inflammation, tissue destruction and repair) and the statistical significance of their relationship with clinically important end points was tested. The selected panel of 24 biomarkers correlated (p,0.01) with forced expiratory volume in 1 s, carbon monoxide transfer factor, 6-minute walk distance, BODE index and exacerbation frequency. Conclusion: PMP technology can be useful in identifying potential biomarkers in patients with COPD. Panels of selected serum markers are associated with important clinical predictors of outcome in these patients.

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“…Consequently, they stimulate the NFBmediated adhesion of leukocytes to endothelial cells and the infiltration of leukocytes into tumors (536). Also, vasoinhibins act as proinflammatory mediators on other cell types, like pulmonary fibroblasts, where they promote the NFB-mediated expression of inducible NOS (iNOS) with potency comparable to the combination of IL-1␤, tumor necrosis factor (TNF)-␣, and interferon (IFN)-␥ (110, 340).…”

Section: Vasoinhibinsmentioning

confidence: 99%

Peptide Hormone Regulation of Angiogenesis

Clapp

Thebault²,

Jeziorski³

et al. 2009

Physiological Reviews

160

158

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It is now apparent that regulation of blood vessel growth contributes to the classical actions of hormones on development, growth, and reproduction. Endothelial cells are ideally positioned to respond to hormones, which act in concert with locally produced chemical mediators to regulate their growth, motility, function, and survival. Hormones affect angiogenesis either directly through actions on endothelial cells or indirectly by regulating proangiogenic factors like vascular endothelial growth factor. Importantly, the local microenvironment of endothelial cells can determine the outcome of hormone action on angiogenesis. Members of the growth hormone/prolactin/placental lactogen, the renin-angiotensin, and the kallikrein-kinin systems that exert stimulatory effects on angiogenesis can acquire antiangiogenic properties after undergoing proteolytic cleavage. In view of the opposing effects of hormonal fragments and precursor molecules, the regulation of the proteases responsible for specific protein cleavage represents an efficient mechanism for balancing angiogenesis. This review presents an overview of the actions on angiogenesis of the above-mentioned peptide hormonal families and addresses how specific proteolysis alters the final outcome of these actions in the context of health and disease.

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16K prolactin induces NF-kappaB activation in pulmonary fibroblasts

Cited by 25 publications

References 15 publications

16-kDa Prolactin Down-Regulates Inducible Nitric Oxide Synthase Expression through Inhibition of the Signal Transducer and Activator of Transcription 1/IFN Regulatory Factor-1 Pathway

16-kDa Prolactin Down-Regulates Inducible Nitric Oxide Synthase Expression through Inhibition of the Signal Transducer and Activator of Transcription 1/IFN Regulatory Factor-1 Pathway

Profiling serum biomarkers in patients with COPD: associations with clinical parameters

Peptide Hormone Regulation of Angiogenesis

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