Expression of human beta-defensins 1 and 2 in kidneys with chronic bacterial infection

Lehmann, Jan; Retz, Margitta; Harder, Jürgen; Krams, Matthias; Kellner, Udo; Hartmann, Julia; Hohgräwe, Kerstin; Raffenberg, Uta; Gerber, Martin; Loch, Tillmann; Weichert-Jacobsen, K.; Stöckle, Michael

doi:10.1186/1471-2334-2-20

Cited by 88 publications

(86 citation statements)

References 27 publications

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“…RT-PCR was performed using SuperScript III First-Strand Synthesis System (Invitrogen, Carlsbad, CA, USA) for the generation of cDNA using equal amounts of total RNA. The following primers were used: for TGF-βRI, 5'-ATGAGCCCCAGCCTTCTCCAT-3', generating a 360-bp product [17].…”

Section: Rna Isolation and Rt-pcrmentioning

confidence: 99%

Transforming growth factor-β1 induces matrix metalloproteinase-9 expression in human meningeal cells via ERK and Smad pathways

Okamoto

Takahashi

Nakamura

et al. 2009

Biochemical and Biophysical Research Communications

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Transforming growth factor (TGF)-β1, a cytokine released into the cerebrospinal fluid (CSF) after intraventricular hemorrhage (IVH), stimulates the expression of the components of the extracellular matrix (ECM), which causes progressive ventricular dilatation by impaired CSF absorption. Matrix metalloproteinase-9 (MMP-9), a proteinase involved in the removal of ECM proteins, has been shown to contribute to the resolution of progressive ventricular dilation after IVH. The aim of this study is to clarify the mechanism by which MMP-9 is expressed following IVH.Cultured human meningeal cells were treated with human recombinant TGF-β1. RT-PCR demonstrated that TGF-β1 induced MMP-9 expression in the meningeal cells in a dose-dependent manner. The TGF-β1-induced MMP-9 expression was attenuated in the presence of either MEK or Smad 3 inhibitor. Our data indicated that MMP-9 is released into the CSF from meningeal cells in response to TGF-β1, most probably through the activation of ERK and Smad pathways. Of these, approximately 15% of the infants require a shunt operation; however, the remaining 85% of the infants exhibit a resolution of ventricular dilation without a shunt operation [1]. The mechanisms for this remain unknown. Thus, elucidating the intrinsic mechanism underlying the resolution of ventricular dilation will contribute to the development of a novel treatment strategy for PHH.Transforming growth factor (TGF)-β1, a cytokine released into the cerebrospinal fluid (CSF) after IVH, is considered to play an important role in the pathogenesis of PHH [2].This cytokine causes progressive ventricular dilation by stimulating the expression of the components of the extracellular matrix (ECM) [3]. In contrast, the removal of ECM is mediated by matrix metalloproteinases (MMPs) [4]. We previously 4 measured MMP-9 activity in the CSF of infants with PHH and showed that there was higher MMP-9 activity in patients who avoided a shunt operation than in patients who required a shunt operation [5]. Thus, our earlier data may indicate that MMP-9 contributes to the resolution of progressive ventricular dilation after IVH. However, the mechanism by which MMP-9 is produced in the CSF of infants with PHH remains to be elucidated. The aim of this study is to clarify the mechanism by which MMP-9 is expressed following IVH.Expression of MMP-9 has been shown to be regulated by various growth factors and cytokines, including TGF-β1 [6][7][8][9]. TGF-β1 stimulates the expression of MMP-9 in various human cell lines through the activation of mitogen-activated protein kinase (MAPK) and/or Smad pathways [6][7][8][9].These data suggest that TGF-β1 may not only play a role in the progression of PHH but also has a beneficial role in the resolution of PHH by enhancing MMP-9 expression.We hypothesized that meningeal cells may be a source of MMP-9 5 production because TGF-β1-mediated deposition of the ECM proteins occurs in the channels of CSF absorption [3]. Here, we show that cultured human meningeal cells express MMP-9 in response to TG...

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Section: Rna Isolation and Rt-pcrmentioning

confidence: 99%

Transforming growth factor-β1 induces matrix metalloproteinase-9 expression in human meningeal cells via ERK and Smad pathways

Okamoto

Takahashi

Nakamura

et al. 2009

Biochemical and Biophysical Research Communications

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“…The fundamental hypothesis is that an additional level of antimicrobial defense must be called into action after infection to complement-constitutive AMP defenses. 19 The strongest evidence that defensins actually play a role in the defense of the kidney comes from studies of a genetically-engineered mouse in which a defensin gene analogous to the constitutively expressed HBD1 was deleted. In contrast to wild-type mice, these null animals do not maintain sterility of their urine; about 30% of the healthy Defb1 Ϫ/Ϫ mice had Staphylococcus species in bladder urine.…”

Section: Defensins and Cathelicidinmentioning

confidence: 99%

Antimicrobial Peptides, Innate Immunity, and the Normally Sterile Urinary Tract

Zasloff¹

2007

Journal of the American Society of Nephrology

196

173

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Considering the anatomical location of the urethral meatus, it is surprising that urine is normally sterile. The defensive properties of uroepithelia help maintain this sterility as strategically necessary for long-term survival. Epithelia lining the urinary tract prevent adhesion of bacteria by release of Tamm-Horsfall protein, lactoferrin, lipocalin, and constitutive and inducible bactericidal antimicrobial peptides such as ␣-and ␤-defensins and cathelicidin. Microbes that overwhelm these early defenses contact uroepithelia and activate an innate immune response through Toll-like receptor 4. With persistence of increasing numbers of microbes, chemokines (IL-8) and cytokines (IL-1 and TNF␣) attract and activate large numbers of neutrophils and macrophages that damage tubulointerstitial parenchyma. The risk of serious infection in humans seems quite variable. Cathelicidin, for example, is a vitamin D-dependent gene, and vitamin D stores may influence susceptibility to urinary tract infection in selected individuals. As more knowledge accrues, vitamin D supplementation may someday be useful as adjuvant therapy in this setting.

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“…The oligonucleotide primers used in the real-time quantitative PCR amplifications are listed in Table 3. The human perforin and H␤D2 primer sequences had been previously reported (28,29).…”

Section: Methodsmentioning

confidence: 99%

The Transcription Factor MEF/Elf4 Is Dually Modulated by p53-MDM2 Axis and MEF-MDM2 Autoregulatory Mechanism

Suico

Fukuda

Miyakita

et al. 2014

Journal of Biological Chemistry

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Background:The ETS transcription factor myeloid elf-1-like factor (MEF) activates some genes including lysozyme, interleukin-8, and MDM2, and also influences the cell cycle. Results: MEF protein expression and stability is suppressed by MDM2 in p53-dependent and -independent manner. Conclusion: MEF is targeted by MDM2 for degradation. Significance: The previously unrecognized MEF-MDM2-p53 axis highlights a regulatory balance of these transcription factors.

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Expression of human beta-defensins 1 and 2 in kidneys with chronic bacterial infection

Cited by 88 publications

References 27 publications

Transforming growth factor-β1 induces matrix metalloproteinase-9 expression in human meningeal cells via ERK and Smad pathways

Transforming growth factor-β1 induces matrix metalloproteinase-9 expression in human meningeal cells via ERK and Smad pathways

Antimicrobial Peptides, Innate Immunity, and the Normally Sterile Urinary Tract

The Transcription Factor MEF/Elf4 Is Dually Modulated by p53-MDM2 Axis and MEF-MDM2 Autoregulatory Mechanism

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