scholarly journals Comparison of In Vitro and In Vivo Antioxidant Activities of Six Flavonoids with Similar Structures

Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 732
Author(s):  
Yixiu Zeng ◽  
Jiajia Song ◽  
Meimei Zhang ◽  
Hongwei Wang ◽  
Yu Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Sulfonic Acid ◽  
Tumor Necrosis ◽  
Antioxidant Activities ◽  
Antioxidative Capacity ◽  
Tnf Α ◽  
Total Antioxidative Capacity ◽  
Necrosis Factor

The in vitro and in vivo antioxidant activities of six flavonoids with similar structures, including epicatechin (EC), epigallocatechin (EGC), procyanidin B2 (P), quercetin (Q), taxifolin (T), and rutin (R) were compared. The structures of the six flavonoids and their scavenging activities for 2,2-diphenyl-1-picrylhydrazyl (DPPH•) and 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+) radicals were closely related. The flavonoids decreased serum contents of malondialdehyde (MDA) and nitric oxide (NO), and increased serum total antioxidative capacity (T-AOC), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) levels to different degrees in d-galactose-treated mice. The changes in mRNA expression of liver GSH-Px1, CAT, SOD1, and SOD2 by d-galactose were dissimilarly restored by the six flavonoids. Moreover, the six flavonoids differentially prevented the inflammatory response caused by oxidative stress by inhibiting interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α levels, and restoring IL-10 levels. These six flavonoids from two subclasses revealed the following antioxidant capability: P > EC, EGC > EC, Q > T, Q > R. Our results indicate that (1) the pyrogallol, dimerization, and C2=C3 double bonds of flavonoids enhanced antioxidant activity and (2) the C3 glycosylation of flavonoids attenuated antioxidant capacity.

Tumor Necrosis Factor-α (TNF-α) Stimulates Chemotactic Response in Mouse Myogenic Cells

2003 ◽  
Vol 12 (1) ◽  
pp. 91-100 ◽  
Author(s):  
Y. Torrente ◽  
E. El Fahime ◽  
N. J. Caron ◽  
R. Del Bo ◽  
M. Belicchi ◽  
...  
Keyword(s):  
Muscle Injury ◽  
Tumor Necrosis ◽  
Chemotactic Activity ◽  
Myogenic Cells ◽  
Tnf Α ◽  
Myoblast Transplantation ◽  
Factor Α ◽  
Necrosis Factor

Migration of transplanted myogenic cells occurs during both embryogenesis and regeneration of skeletal muscles and is important for successful myoblast transplantation, but little is known about factors that promote chemotaxis of these cells. Tumor necrosis factor-α (TNF-α) is known to induce chemotactic effect on several cell types. In this study, we investigated its influence on the in vitro and in vivo motility of C2C12 and primary myoblasts. In the in vitro test performed in the blind-well Boyden chambers, we showed that TNF-α (50–400 U/ml) significantly enhanced the ability of myogenic cells to migrate. The dose–response curve for this factor was bell shaped, with maximum activity in the 200 U/ml range. In the in vivo test, intramuscular administration of TNF-α was performed by an Alzet pump connected to a perforated polyethylene microtube inserted in the tibialis anterior (TA) of CD1 mice. In these experiments, myoblasts were injected under the muscle epimysium. The recipient mice were immunosuppressed with FK506. Our results showed that, 5 days after myoblast transplantation, cells migrated further in the muscles infused with TNF-α than in the muscles not exposed to TNF-α. TNF-α not only has a chemotactic activity but may also modify cell migration via its action on matrix metalloproteinase (MMP) expression. The proteolytic activities of the MMPs secreted in the muscles were thus also assessed by gelatin zymography. The results showed an increased of MMP-2 and MMP-9 transcripts in the TNF-α-infused muscles injected with myogenic cells. Myoblast migration during transplantation may be enhanced by overlapping gradients of several effector molecules such as TNF-α, interferon-γ (INF-γ), and interleukins, released at the site of muscle injury. We propose that TNF-α may promote myoblast migration directly through chemotactic activity and indirectly by enhancing MMP activity at the site of muscle injury.

scholarly journals Lipoxin (LX)A4 and Aspirin-triggered 15-epi-LXA4 Inhibit Tumor Necrosis Factor 1α–initiated Neutrophil Responses and Trafficking: Regulators of a Cytokine–Chemokine Axis

1999 ◽  
Vol 189 (12) ◽  
pp. 1923-1930 ◽  
Author(s):  
Mohamed Hachicha ◽  
Marc Pouliot ◽  
Nicos A. Petasis ◽  
Charles N. Serhan
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Gm Csf ◽  
Tnf Α ◽  
Human Polymorphonuclear Leukocytes ◽  
The Impact ◽  
Receptor Antibodies ◽  
Necrosis Factor

The impact of  lipoxin A4 (LXA4) and aspirin-triggered lipoxins (ATLs) was investigated in tumor necrosis factor (TNF)-α–initiated neutrophil (polymorphonuclear leukocyte) responses in vitro and in vivo using metabolically stable LX analogues. At concentrations as low as 1–10 nM, the LXA4 and ATL analogues each inhibited TNF-α–stimulated superoxide anion generation and IL-1β release by human polymorphonuclear leukocytes. These LXA4-ATL actions were time and concentration dependent and proved selective for TNF-α, as these responses were not altered with either GM-CSF– or zymosan-stimulated cells. TNF-α–induced IL-1β gene expression was also regulated by both anti-LXA4 receptor antibodies and LXA4-ATL analogues. In murine air pouches, 15R/S-methyl-LXA4 dramatically inhibited TNF-α–stimulated leukocyte trafficking, as well as the appearance of both macrophage inflammatory peptide 2 and IL-1β, while concomitantly stimulating IL-4 in pouch exudates. Together, these results indicate that both LXA4 and ATL regulate TNF-α–directed neutrophil actions in vitro and in vivo and stimulate IL-4 in exudates, playing a pivotal role in immune responses.

scholarly journals Differential Tumor Necrosis Factor Alpha Expression and Release from Peritoneal Mouse Macrophages In Vitro in Response to Proliferating Gram-Positive versus Gram-Negative Bacteria

2000 ◽  
Vol 68 (8) ◽  
pp. 4422-4429 ◽  
Author(s):  
Wei Cui ◽  
David C. Morrison ◽  
Richard Silverstein
Keyword(s):  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Gram Negative ◽  
E Coli ◽  
Tnf Α ◽  
Mouse Macrophages ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Viable Escherichia coli and Staphylococcus aureus bacteria elicited markedly different in vitro tumor necrosis factor alpha (TNF-α) responses when placed in coculture with peritoneal murine macrophages. These include quantitative differences in TNF-α mRNA expression and corresponding protein product secretion as well as kinetic differences in the profiles of the TNF-α responses. Further, lipopolysaccharide (from E. coli) is a major contributing factor to these differences, as revealed by comparative experiments with endotoxin-responsive (C3Heb/FeJ) and endotoxin-hyporesponsive (C3H/HeJ) macrophages. Nevertheless, the eventual overall magnitude of the TNF-α secretion of macrophages in response to S. aureus was at least equivalent to that observed with E. coli, while appearing at time periods hours later than the E. coli-elicited TNF-α response. Both the magnitude and kinetic profile of the TNF-α responses were found to be relatively independent of the rate of bacterial proliferation, at least to the extent that similar results were observed with both viable and paraformaldehyde-killed microbes. Nevertheless, S. aureus treated in culture with the carbapenem antibiotic imipenem manifests markedly altered profiles of TNF-α response, with the appearance of an early TNF-α peak not seen with viable organisms, a finding strikingly similar to that recently reported by our laboratory from in vivo studies (R. Silverstein, J. G. Wood, Q. Xue, M. Norimatsu, D. L. Horn, and D. C. Morrison, Infect. Immun. 68:2301–2308, 2000). In contrast, imipenem treatment of E. coli-cocultured macrophages does not significantly alter the observed TNF-α response either in vitro or in vivo. In conclusion, our data support the concept that the host inflammatory response of cultured mouse macrophages in response to viable gram-positive versus gram-negative microbes exhibits distinctive characteristics and that these distinctions are, under some conditions, altered on subsequent bacterial killing, depending on the mode of killing. Of potential importance, these distinctive in vitro TNF-α profiles faithfully reflect circulating levels of TNF-α in infected mice. These results suggest that coculture of peritoneal macrophages with viable versus antibiotic-killed bacteria and subsequent assessment of cytokine response (TNF-α) may be of value in clarifying, and ultimately controlling, related host inflammatory responses in septic patients.

scholarly journals Cimifugin ameliorates imiquimod-induced psoriasis by inhibiting oxidative stress and inflammation via NF-κB/MAPK pathway

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Aimin Liu ◽  
Wei Zhao ◽  
Buxin Zhang ◽  
Yuanhui Tu ◽  
Qingxing Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Diseases ◽  
Mapk Pathway ◽  
Severity Index ◽  
Mapk Signaling ◽  
Psoriasis Area Severity Index ◽  
Tnf Α ◽  
Necrosis Factor

Abstract Cimifugin is an important component of chromones in the dry roots of Saposhikovia divaricata for treating inflammatory diseases. However, the possible effect of cimifugin in psoriasis needs further investigation. This current work was designed to evaluate the effects of cimifugin in psoriasis in vivo and in vitro, and unravel the underlying molecular mechanism. Here, we used imiquimod (IMQ) or tumor necrosis factor (TNF)-α to induce a psoriasis-like model in mice or keratinocytes. Obviously, the results showed that cimifugin reduced epidermal hyperplasia, psoriasis area severity index (PASI) scores, ear thickness and histological psoriasiform lesions in IMQ-induced mice. The decreased levels of reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT), and the accumulation of malondialdehyde (MDA) in skin tissues by IMQ were attenuated by cimifugin. Furthermore, it was observed that cimifugin effectively reversed IMQ-induced up-regulation of proinflammatory cytokines, including TNF-α, IL-6, IL-1β, IL-17A, and IL-22. Mechanically, we noticed that cimifugin inhibited IMQ-activated phosphorylation of NF-κB (IκB and p65) and MAPK (JNK, ERK, and p38) signaling pathways. Similar alterations for oxidative stress and inflammation parameters were also detected in TNF-α-treated HaCaT cells. In addition, cimifugin-induced down-regulation of ICAM-1 were observed in TNF-α-treated cells. Altogether, our findings suggest that cimifugin protects against oxidative stress and inflammation in psoriasis-like pathogenesis by inactivating NF-κB/MAPK signaling pathway, which may develop a novel and effective drug for the therapy of psoriasis.

Oxyresveratrol dampens neuroimmune responses in vivo: a selective effect on TNF-α

2006 ◽  
Vol 291 (5) ◽  
pp. R1215-R1221 ◽  
Author(s):  
A. Mouihate ◽  
T. F. Horn ◽  
Q. J. Pittman
Keyword(s):  
Tumor Necrosis ◽  
Inflammatory Responses ◽  
Inhibitory Effect ◽  
Febrile Response ◽  
Pathological Conditions ◽  
Tnf Α ◽  
Cytokine Tumor Necrosis Factor ◽  
Necrosis Factor

Consumption of nutrients rich in hydroxystilbenes has been promoted because of their health benefits, including dampening of inflammatory responses. However, few studies have examined their effects in vivo. Here, we show that the hydroxystilbene oxyresveratrol (trans-2,3′,4,5′-tetrahydroxystilbene: o-RES) blocked hypothermia but caused no significant effect on the febrile response to the immune stimulus, bacterial LPS in rats. This was associated with a reduction in the LPS-induced plasma cytokine, tumor necrosis factor (TNF)-α, but not IL-6. Both IL-6-stimulated STAT-3 and LPS-induced cycoloxygenase-2 expression in the hypothalamus were not affected by o-RES. These data strongly suggest that the o-RES-induced dampening of neuroimmune responses is largely due to its inhibitory effect on TNF-α production. In contrast to in vitro experiments, o-RES has no direct effect on NF-κB signaling pathway in vivo. The specific inhibitory effect of o-RES on TNF-α opens new avenues for the clinical use of o-RES in pathological conditions where excessive production of TNF-α is deleterious.

scholarly journals Anomalous Role of Tumor Necrosis Factor Alpha in Experimental Enterococcal Infection

2002 ◽  
Vol 70 (12) ◽  
pp. 6628-6637 ◽  
Author(s):  
Christopher J. Papasian ◽  
Richard Silverstein ◽  
Jian Jun Gao ◽  
David M. Bamberger ◽  
David C. Morrison
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Potential Contribution ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT The murine d-galactosamine (d-gal) model of tumor necrosis factor alpha (TNF-α) hypersensitization was used as an initial tool to investigate the potential contribution of TNF-α to lethal intraperitoneal (i.p.) infection with Enterococcus faecalis. d-gal sensitized mice to lethal E. faecalis infection, whereas dexamethasone and neutralizing anti-TNF-α antibody protected d-gal-treated, E. faecalis-infected mice, implicating TNF-α in the lethal response to E. faecalis infection in d-gal-treated mice. Circulating TNF-α was undetectable for at least 8 h following i.p. E. faecalis infection, although low peritoneal levels of TNF-α were detected within 3 h, suggesting that localized TNF-α production contributed to the lethal response to E. faecalis infection in d-gal-treated mice. Although i.p. E. faecalis infection failed to induce a detectable systemic TNF-α response, circulating Interleukin-6 (IL-6) was detected within 3 h of infection. IL-6 was also detected in the peritoneum within an hour of infection, prior to the appearance of peritoneal TNF-α. In striking contrast to in vivo results, E. faecalis induced a potent and rapid TNF-α response from both mouse peritoneal macrophages and the RAW 264.7 cell line in vitro. This led us to hypothesize that TNF-α production in response to E. faecalis infection is suppressed by IL-6 in vivo. In vitro experiments demonstrated a statistically significant, but modest, inhibitory effect of IL-6 on TNF-α production by RAW cells stimulated with E. faecalis. Collectively, these data indicate that acute, lethal E. faecalis infection appears to induce an unusual cytokine response that differs in character from that previously described for most other gram-positive and gram-negative bacteria.

scholarly journals Μελέτη του ρόλου του κυτταροσκελετού της δεσμίνης στην ανεύρεση νέων μηχανισμών καρδιομυοπροστασίας

2008 ◽  
Author(s):  
Παναγιώτα Παναγοπούλου
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tnf Α ◽  
Necrosis Factor ◽  
Area Composita

Η δεσμίνη, η μυοειδική πρωτεΐνη των ενδιαμέσων ινιδίων, δημιουργεί ένα εκτενές δίκτυο που συνδέει τη συσταλτή συσκευή των μυοκυττάρων με την κυτταροπλασματική μεμβράνη -στο επίπεδο των εμβόλιμων δίσκων για τα καρδιομυοκύτταρα- τον πυρήνα και διάφορα μεμβρανώδη κυτταρικά οργανίδια. Σκοπός αυτής της εργασίας ήταν η διερεύνηση του μηχανισμού καρδιοπροστασίας που παρέχει ο κυτταροσκελετός της δεσμίνης in vivo, καθώς και η γενικότερη συμμετοχή της στα μονοπάτια της απόπτωσης. Η αποδιοργάνωση του κυτταροσκελετού είναι μια βασική διαδικασία για την εξέλιξη του μονοπατιού της απόπτωσης. Τόσο τα μικροϊνίδια της ακτίνης, όσο και τα ενδιάμεσα ινίδια -συμπεριλαμβανομένων και των πυρηνικών λαμινών- αποτελούν υπόστρωμα πέψης για διάφορα μέλη της οικογένειας των κασπασών. Η δεσμίνη είναι γνωστό ότι πέπτεται in vitro από ανασυνδυασμένη κασπάση-6, στο 263 ασπαρτικό οξύ. Το αμινοτελικό προϊόν αυτής της πέψης δεν είναι ικανό να συμμετέχει στη συγκρότηση ινιδίων, αλλά αντίθετα παρεμποδίζει αυτή τη διαδικασία σχηματίζοντας συσσωματώματα. Ως in vivo μοντέλο επαγωγής της απόπτωσης χρησιμοποιήθηκαν διαγονιδιακά ποντίκια που υπερεκφράζουν, ειδικά στην καρδιά, τον Παράγοντα Νέκρωσης Όγκων (Tumor Necrosis Factor, TNF-α). O TNF-α έχει βρεθεί ότι επάγει διαφορετικά μονοπάτια κυτταρικού θανάτου ενεργοποιώντας, μεταξύ άλλων, μέλη της οικογένειας των πρωτεολυτικών ενζύμων, των κασπασών. Το μυοκάρδιο των ποντικιών που υπερεκφράζει TNF-α (ΜΗCsTNF) χαρακτηρίζεται αρχικά από ομόκεντρη υπερτροφία των καρδιομυοκυττάρων που ακολουθείται από διάταση τόσο των κόλπων, όσο και των κοιλιών. Τα ποντίκια αυτά πεθαίνουν από καρδιακή ανεπάρκεια σε ποσοστό 25% πριν τη συμπλήρωση του έκτου μήνα ζωής. Στο μυοκάρδιο των ΜΗCsTNF ποντικιών ελέγχθηκε αρχικά ο υποκυτταρικός εντοπισμός της δεσμίνης. Η δεσμίνη στην καρδιά των ΜΗCsTNF ποντικιών έχει χάσει τον εντοπισμό της στους εμβόλιμους δίσκους, αλλά διατηρεί, εν μέρει, την παρουσία της στους Ζ-δίσκους. Προκειμένου να διαπιστωθεί εάν εκτός από τη δεσμίνη, έχει αλλοιωθεί η παρουσία και άλλων πρωτεϊνών των εμβόλιμων δίσκων, μελετήθηκε στο μυοκάρδιο αυτών των ποντικιών, η υποκυτταρική κατανομή της δεσμοπλακίνης, της β-κατενίνης και της κοννεξίνης 43, που είναι χαρακτηριστικές πρωτεΐνες των δεσμοσωμάτων, των συνδέσμων πρόσδεσης και των χασματοσυνδέσμων, αντίστοιχα. Οι πρωτεΐνες αυτές αρχικά φαίνεται να αγκυροβολούνται στους εμβόλιμους δίσκους, παροδικά όμως απομακρύνονται και κατευθύνονται προς την πλευρική επιφάνεια των καρδιομυοκυττάρων. Μελέτη με ηλεκτρονικό μικροσκόπιο αποκάλυψε ότι εκτός από την κατανομή συγκεκριμένων πρωτεϊνών, είναι διαταραγμένη και η γενική αρχιτεκτονική των εμβόλιμων δίσκων. Επιπρόσθετα, πιστοποιήθηκε ότι η δεσμίνη πέπτεται in vivo και συσσωρεύεται σε συσσωματώματα. Η παρουσία συσσωματωμάτων δεσμίνης έχει συσχετιστεί με αρκετές κληρονομικές μυοπάθειες στον άνθρωπο, οι οποίες χαρακτηρίζονται ως Μυοπάθειες Σχετιζόμενες με τη Δεσμίνη (Desmin Related Myopathies, DRM). Μεταλλάξεις, αλλά και τροποποιήσεις στη δεσμίνη ή σε άλλες πρωτεΐνες με τις οποίες αλληλεπιδρά προκειμένου να δημιουργήσει το συνεχόμενο κυτταροσκελετικό δίκτυο, έχουν ως συνέπεια τη συγκέντρωση συσσωματωμάτων στο κυτταρόπλασμα και έχουν ενοχοποιηθεί για τη διατατική μυοκαρδιοπάθεια και την εξέλιξη της καρδιακής ανεπάρκειας. Στο μυοκάρδιο των ΜΗCsTNF ποντικιών πιστοποιήθηκε η παρουσία δύο διαφορετικών ειδών συσσωματωμάτων της δεσμίνης. Τα πρώτα εμφανίζουν διάχυτο κυτταροπλασματικό πρότυπο και η δεσμίνη σε αυτά συνεντοπίζεται με την HSP25, ενώ τα δεύτερα τείνουν να περιοριστούν κοντά στον πυρήνα και εδώ η δεσμίνη συνεντοπίζεται με την ουμπικουϊτίνη. Μελέτη της υπερδομής των συσσωματωμάτων έδειξε ότι ποικίλουν σε μέγεθος και σύσταση, καθώς περιέχουν κυστίδια, μιτοχόνδρια, μεμβρανώδες υλικό και υλικό υψηλής πυκνότητας, που φαίνεται ότι παρεμποδίζουν, εκτός από τη λειτουργία του πρωτεασώματος, την συσταλτική ικανότητα των μυοϊνιδίων και συμβάλλουν στην εξέλιξη της καρδιακής ανεπάρκειας. Προκειμένου να μελετηθεί η σπουδαιότητα της δεσμίνης στην παθολογία του μυοκαρδίου που υπερεκφράζει TNF-α, ΜΗCsTNF ποντίκια διασταυρώθηκαν με ποντίκια που δεν εκφράζουν δεσμίνη (des-/-). Τα des-/- ποντίκια χαρακτηρίζονται από μια παροδική υπερτροφία των καρδιομυοκυττάρων, η οποία ακολουθείται από ανάπτυξη διατατικής μυοκαρδιοπάθειας με εξέχοντα χαρακτηριστικά τις ανωμαλίες στα μιτοχόνδρια, το μαζικό κυτταρικό θάνατο και τις εκτενείς εναποθέσεις ασβεστίου στην εξωτερική επιφάνεια της καρδιάς και κολλαγόνου στο εσωτερικό της. Τα ΜΗCsTNF des-/- ποντίκια παρουσίασαν δραματική μείωση και στις δύο μορφές συσσωματωμάτων, ενώ η δεσμοπλακίνη και η β-κατενίνη -πρωτεΐνες που ανήκουν σε μια ενιαία και διαπλεκόμενη μορφή κυτταρικών συνδέσεων, την “area composita”- διατήρησαν σημαντικά την παρουσία τους στους εμβόλιμους δίσκους. Οι παρατηρήσεις αυτές υπογραμμίζουν το βαθμό στον οποίο η δεσμίνη συμμετέχει στην εξέλιξη του ΜΗCsTNF φαινοτύπου. Παραδόξως, στο μυοκάρδιο των ΜΗCsTNF des-/- ποντικιών δεν παρατηρούνται τα μορφολογικά χαρακτηριστικά που προκαλεί η έλλειψη της δεσμίνης, ενώ διατηρούνται αυτά της υπερέκφρασης του TNF-α, υποδηλώνοντας ενδεχόμενη προστατευτική δράση του TNF-α για τα des-/- καρδιομυοκύτταρα. Η διερεύνηση του μηχανισμού της πέψης της δεσμίνης από την κασπάση-6, αλλά και της απομάκρυνσής της από τους εμβόλιμους δίσκους, με τις συνακόλουθες συνέπειες, αποτέλεσε τον επόμενο στόχο αυτής της εργασίας. Για το σκοπό αυτό, δημιουργήθηκαν διαγονιδιακά ποντίκια που εκφράζουν τη μεταλλαγμένη δεσμίνη D263E, η οποία στο 263 αμινοξύ φέρει αντί για ασπαρτικό, γλουταμινικό οξύ. Η D263E δεσμίνη δεν πέπτεται από τις κασπάσες στο ΜΗCsTNF μυοκάρδιο, διατηρεί σε μεγάλο βαθμό την παρουσία της στους εμβόλιμους δίσκους και φαίνεται ότι συγκρατεί και τις υπόλοιπες πρωτεΐνες της “area composita” στη δομή αυτή. Επιπλέον, τα συσσωματώματα της ουμπικουϊτίνης μειώνονται σημαντικά και χάνεται ο συνεντοπισμός με τη δεσμίνη σε όσα από αυτά σχηματίζονται. Τέλος, η παρουσία της D263E δεσμίνης μείωσε τον αριθμό των αποπτωτικών καρδιομυοκυττάρων στο ΜΗCsTNF μυοκάρδιο και βελτίωσε σημαντικά την καρδιακή λειτουργία. Συνοψίζοντας, τα αποτελέσματα αυτής της εργασίας υπογραμμίζουν ότι η δεσμίνη είναι ένα μόριο με σημαντικό ρόλο στην εξέλιξη της μυοκαρδιοπάθειας και της καρδιακής ανεπάρκειας, στο μοντέλο που προκαλείται από την υπερέκφραση του TNF-α. Η συμμετοχή της στο μονοπάτι της απόπτωσης ως υπόστρωμα πέψης για τις κασπάσες και οι επακόλουθες συνέπειες, αποτελούν βάση μελέτης του ρόλου των ενδιαμέσων ινιδίων και για άλλες εκφυλιστικές νόσους.

scholarly journals CXCR2- and E-Selectin–induced Neutrophil Arrest during Inflammation In Vivo

2004 ◽  
Vol 200 (7) ◽  
pp. 935-939 ◽  
Author(s):  
Michael L. Smith ◽  
Timothy S. Olson ◽  
Klaus Ley
Keyword(s):  
Monoclonal Antibody ◽  
Tumor Necrosis ◽  
In Vitro Assays ◽  
Neutrophil Adhesion ◽  
Cremaster Muscle ◽  
Wild Type ◽  
Tnf Α ◽  
Necrosis Factor

The signaling events leading to the activation of integrins and firm arrest of rolling neutrophils in inflamed venules have yet to be elucidated. In vitro assays suggest that both E-selectin and chemokines can trigger arrest of rolling neutrophils, but E-selectin−/− mice have normal levels of adherent neutrophils in inflamed venules. To test whether chemokine-induced neutrophil arrest in vivo can be unmasked by blocking E-selectin, we investigated neutrophil adhesion in inflamed cremaster muscle venules in tumor necrosis factor (TNF)-α–treated CXCR2−/− or wild-type (WT) mice injected with E-selectin blocking monoclonal antibody (mAb) 9A9. To block chemokine receptor signaling, we investigated E-selectin−/− or WT mice treated with pertussis toxin (PTx) intravenously. Neutrophil adhesion was unchanged in CXCR2−/−, E-selectin−/−, PTx-treated WT, or mAb 9A9–treated WT mice. However, TNF-α–induced neutrophil adhesion was almost completely abrogated in E-selectin−/− mice treated with PTx and significantly reduced in CXCR2−/− mice treated with the E-selectin blocking mAb. In thioglycollate-induced peritonitis, PTx treatment blocked neutrophil recruitment into the peritoneum of E-selectin−/− mice, but had only a partial effect in WT animals. These data show that E-selectin– and chemokine-mediated arrest mechanisms are overlapping in this model and identify CXCR2 as an important neutrophil arrest chemokine in vivo.

scholarly journals Terpene Glycosides from Sanguisorba officinalis and Their Anti-Inflammatory Effects

Molecules ◽  
2019 ◽  
Vol 24 (16) ◽  
pp. 2906 ◽  
Author(s):  
Da-Le Guo ◽  
Jin-Feng Chen ◽  
Lu Tan ◽  
Meng-Ying Jin ◽  
Feng Ju ◽  
...  
Keyword(s):  
Tumor Necrosis ◽  
High Resolution Mass Spectrometry ◽  
Experimental Platform ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Sanguisorba Officinalis ◽  
Factor Α ◽  
Necrosis Factor

Two new terpene glycosides (1–2) along with two known analogs (3–4) were obtained from the root of Sanguisorba officinalis, which is a common traditional Chinese medicine (TCM). Their structures were elucidated by nuclear magnetic resonance (NMR), electrospray ionization high resolution mass spectrometry (HRESIMS), and a hydrolysis reaction, as well as comparison of these data with the literature data. Compounds 1–4 exhibited anti-inflammatory properties in vitro by attenuating the production of inflammatory mediators, such as nitric oxide (NO) as well as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). An anti-inflammatory assay based on the zebrafish experimental platform indicated that compound 1 had good anti-inflammatory activity in vivo by not only regulating the distribution, but also by reducing the amount of the macrophages of the zebrafish exposed to copper sulfate.

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