Metalloproteinases TACE and MMP-9 Differentially Regulate Death Factors on Adult and Neonatal Monocytes After Infection with Escherichia coli.

Published on Mar 20, 2019in International Journal of Molecular Sciences5.924
· DOI :10.3390/IJMS20061399
Stephan Dreschers7
Estimated H-index: 7
(Boston Children's Hospital),
Christopher Platen4
Estimated H-index: 4
(Boston Children's Hospital)
+ 3 AuthorsThorsten W. Orlikowsky16
Estimated H-index: 16
(Boston Children's Hospital)
Background: Cleaving ligands and receptors of the tumor necrosis factor (TNF) superfamily can critically regulate the induction of apoptosis. Matrix metalloproteinases (MMPs) such as MMP-9 and tumor necrosis factor-α-converting enzyme (TACE) have been shown to cleave CD95-Ligand (CD95L) and TNF/(TNF receptor-1) TNFR1 which induce phagocytosis induced cell death (PICD) in adult monocytes. This process is reduced in neonatal monocytes. Methods: Here we tested in vitro, whether Escherichia coli infection mounts for activation of MMP-9 and TACE in monocytes and whether this process regulates PICD. Results: The surface expression of TACE was most prominent on infected adult monocytes. In contrast, surface presentation of MMP-9 was highest on infected neonatal monocytes. Selective blocking of MMP-9 decreased CD95L secretion, while inhibition of TACE left CD95L secretion unaltered. Blocking of MMP-9 increased surface CD95L (memCD95L) expression on infected neonatal monocytes to levels comparable to infected adult monocytes. Moreover, MMP-9 inhibition raised PICD of infected neonatal monocytes to levels observed for infected adult monocytes. In contrast, TACE inhibition decreased PICD in infected monocytes. Addition of extracellular TNF effectively induced memCD95L presentation and PICD of adult monocytes and less of neonatal monocytes. Conclusion: MMP-9 activity is crucial for downregulating cell-contact dependent PICD in E. coli infected neonatal monocytes. By this mechanism, MMP-9 could contribute to reducing sustained inflammation in neonates.
📖 Papers frequently viewed together
#1Robert H. Scannevin (Janssen Pharmaceutica)H-Index: 29
#2Richard Alexander (Janssen Pharmaceutica)H-Index: 6
Last. Lawrence C. Kuo (Janssen Pharmaceutica)H-Index: 2
view all 24 authors...
Abstract Aberrant activation of matrix metalloproteinases (MMPs) is a common feature of pathological cascades observed in diverse disorders, such as cancer, fibrosis, immune dysregulation, and neurodegenerative diseases. MMP-9, in particular, is highly dynamically regulated in several pathological processes. Development of MMP inhibitors has therefore been an attractive strategy for therapeutic intervention. However, a long history of failed clinical trials has demonstrated that broad-spectrum M...
#1Emily K. Stinemetz (University of Texas Health Science Center at Houston)H-Index: 1
#2Peng Gao (University of Texas Health Science Center at Houston)H-Index: 18
Last. Barrett R. Harvey (University of Texas Health Science Center at Houston)H-Index: 3
view all 6 authors...
AtlA is the major peptidoglycan hydrolase of Enterococcus faecalis involved in cell division and cellular autolysis. The secreted zinc metalloprotease, gelatinase (GelE), has been identified as an important regulator of cellular function through post-translational modification of protein substrates. AtlA is a known target of GelE, and their interplay has been proposed to regulate AtlA function. To study the protease-mediated post-translational modification of AtlA, monoclonal antibodies were dev...
#1Stephan Dreschers (Boston Children's Hospital)H-Index: 7
#2Christian GilleH-Index: 17
Last. Thorsten W. OrlikowskyH-Index: 16
view all 6 authors...
Phagocytosis-induced cell death (PICD) is diminished in cord blood monocytes (CBMO) as compared to cells from adults (PBMO) due to differences in the CD95-pathway. This may support a prolonged pro-inflammatory response with sequels of sustained inflammation as seen in neonatal sepsis. Here we hypothesized that TNF-α mediated induction of apoptosis is impaired in CBMO due to differences in the TNFR1-dependent internalization. Monocytes were infected with Escherichia coli-GFP (E. coli-GFP). Monocy...
#1Rima TapaderH-Index: 6
#2Dipro Bose (VIT University)H-Index: 8
Last. Amit PalH-Index: 11
view all 3 authors...
Abstract YghJ, also known as SslE (Secreted and surface associated lipoprotein) is a cell surface associated and secreted lipoprotein harbouring M60 metalloprotease domain. Though the gene is known to be conserved among both pathogenic and commensal Escherichia coli isolates, the expression and secretion of YghJ was found to be higher among diverse E. coli pathotypes. YghJ, secreted from intestinal pathogens such as enterotoxigenic E. coli (ETEC) and enteropathogenic E. coli (EPEC) has been demo...
#1Priya Sakthivel (Otto-von-Guericke University Magdeburg)H-Index: 6
#2Angele Breithaupt (FU: Free University of Berlin)H-Index: 22
Last. Dunja Bruder (Otto-von-Guericke University Magdeburg)H-Index: 28
view all 9 authors...
Background COPD represents a multifactorial lung disorder with high morbidity and mortality. Despite intensive research concerning the underlying disease mechanisms, the involvement of the CD200/CD200R axis in supporting or preventing the onset of COPD has not yet been addressed. Since the CD200/CD200R axis is crucially implicated in the maintenance of pulmonary immune homeostasis, we hypothesized that it might be involved in controlling the onset of COPD.
#1Mashael F. Alqahtani (NU: Northwestern University)H-Index: 2
#2Craig M. Smith (NU: Northwestern University)H-Index: 11
Last. Mark S. Wainwright (NU: Northwestern University)H-Index: 30
view all 6 authors...
Elevated plasma concentrations of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), mid-regional pro-atrial natriuretic peptide (mrProANP), and adipocyte fatty-acid-binding proteins (A-FaBPs) have been investigated as biomarkers for sepsis or detection of acute neurological injuries in adults, but not children. We carried out a single-center, prospective observational study to determine if these measures could serve as biomarkers to identify children with seps...
AbstractObjective: To investigate the role of matrix metalloproteinases (MMP-2, MMP-9) and their inducer (CD147) in premature rupture of membranes (PROM) at term labor.Methods: In a cross-sectional study, 24 women aged 19–39, with 37–40-week pregnancy, and no clinical and histological signs of chorioamnionitis, were divided into two groups with and without PROM. The histological and immunohistochemical study of the fetal membranes was performed with polyclonal rabbit antibodies to MMP-2/MMP-9 an...
#1Manoj Muthukuru (WVU: West Virginia University)H-Index: 8
#2Christopher W. Cutler (Georgia Regents University)H-Index: 18
Inflammatory cytokines activate tissue collagenases such as matrix metalloproteinases (MMPs). MMPs are antagonized by tissue inhibitors of metalloproteinases (TIMPs) that attempt to regulate excessive collagenase activity during inflammatory conditions. During chronic inflammatory conditions, induction of endotoxin tolerance negatively regulates the cytokine response in an attempt to curtail excessive host tissue damage. However, little is known about how downregulation of inflammatory cytokines...
#1Eleni Papakonstantinou (A.U.Th.: Aristotle University of Thessaloniki)H-Index: 26
#2George Karakiulakis (A.U.Th.: Aristotle University of Thessaloniki)H-Index: 26
Last. Daiana StolzH-Index: 38
view all 7 authors...
Background Acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) are associated with accelerated aggravation of clinical symptoms and deterioration of pulmonary function. The mechanisms by which exacerbations may contribute to airway remodeling and declined lung function are poorly understood. In this study, we investigated if AE-COPD are associated with differential expression of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in bronchoalveolar lavage (BAL...
#1Olaf Dammann (MHH: Hannover Medical School)H-Index: 70
#2Alan Leviton (Boston Children's Hospital)H-Index: 92
Exposure to perinatal infection and inflammation is associated with an increased risk for neonatal brain damage and developmental disabilities. In this integrated mechanism review, we discuss evidence in support of the contention that the preterm newborn is capable of intermittent or sustained systemic inflammation (ISSI), which appears to contribute more to adverse neurodevelopmental outcomes in preterm infants than does shorter duration inflammation.
Cited By2
#1Jie LiuH-Index: 1
#2Guang-Yu ZhangH-Index: 2
Last. You-Zhi TangH-Index: 15
view all 11 authors...
A class of pleuromutilin derivatives containing 1, 3, 4-oxadiazole were designed and synthesized as potential antibacterial agents against Methicillin-resistant staphylococcus aureus (MRSA). The ultrasound-assisted reaction was proposed as a green chemistry method to synthesize 1, 3, 4-oxadiazole derivatives (intermediates 85-110). Among these pleuromutilin derivatives, compound 133 was found to be the strongest antibacterial derivative against MRSA (MIC = 0.125 μg/mL). Furthermore, the result o...
#1Anke SeifertH-Index: 4
#2Andreas LudwigH-Index: 43
view all 3 authors...
#1Magnus S. Ågren (UCPH: University of Copenhagen)H-Index: 8
#2Ulrich auf dem Keller (DTU: Technical University of Denmark)H-Index: 35
Zinc-dependent matrix metalloproteinases (MMPs) belong to metzincins that comprise not only 23 human MMPs but also other metalloproteinases, such as 21 human ADAMs (a disintegrin and metalloproteinase domain) and 19 secreted ADAMTSs (a disintegrin and metalloproteinase thrombospondin domain). The many setbacks from the clinical trials of broad-spectrum MMP inhibitors for cancer indications in the late 1990s emphasized the extreme complexity of the participation of these proteolytic enzymes in bi...
This website uses cookies.
We use cookies to improve your online experience. By continuing to use our website we assume you agree to the placement of these cookies.
To learn more, you can find in our Privacy Policy.