scholarly journals Ambient but not incremental oxidant generation effects intercellular adhesion molecule 1 induction by tumour necrosis factor α in endothelium

1998 ◽  
Vol 331 (3) ◽  
pp. 853-861 ◽  
Author(s):  
Toshiyuki ARAI ◽  
Susan A. KELLY ◽  
Matthew L. BRENGMAN ◽  
Manabu TAKANO ◽  
Elise H. SMITH ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Adhesion Molecule ◽  
Tumour Necrosis ◽  
Intercellular Adhesion Molecule ◽  
Tumour Necrosis Factor Α ◽  
Intercellular Adhesion Molecule 1 ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Proinflammatory cytokines upregulate endothelial adhesion molecule expression, thereby initiating the microvascular inflammatory response. We re-evaluated the reported role of reactive oxygen metabolites (ROMs) in signalling upregulation of intercellular adhesion molecule 1 (ICAM-1) on endothelial cells by tumour necrosis factor α (TNF-α) in vitro. TNF-α upregulation of endothelial-cell ICAM-1 expression was inhibited by the cell-permeable antioxidants, or by the adenovirus-mediated intracellular overexpression of Cu,Zn-superoxide dismutase, but not by the exogenous (extracellular) administration of the cell-impermeable antioxidants, superoxide dismutase and/or catalase. This ICAM-1 upregulation was also inhibited by inhibitors of NADH dehydrogenase, cytochrome bc1 complex and NADPH oxidase. However, a measurable increase in net cellular ROM generation in response to TNF-α was not seen using four disparate sensitive ROM assays. Moreover, the stimulation of exogenous or endogenous ROM generation did not upregulate ICAM-1, nor enhance ICAM-1 upregulation by TNF-α. These findings suggest that an ambient background flux of ROMs, generated intracellularly, but not their net incremental generation, is necessary for TNF-α to induce ICAM-1 expression in endothelium in vitro.

scholarly journals The effects of tumour necrosis factor-α and interleukin1 on an in vitro model of thyroid-associated ophthalmopathy; contrasting effects on adipogenesis

2006 ◽  
Vol 155 (3) ◽  
pp. 395-403 ◽  
Author(s):  
T J Cawood ◽  
P Moriarty ◽  
C O’Farrelly ◽  
D O’Shea
Keyword(s):  
Hyaluronic Acid ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Intercellular Adhesion Molecule ◽  
Tumour Necrosis Factor Α ◽  
Intercellular Adhesion Molecule 1 ◽  
Thyroid Associated Ophthalmopathy ◽  
Factor Α ◽  
Necrosis Factor

Objective: Cytokines are likely to play a key pathogenic role in thyroid-associated ophthalmopathy (TAO). Anti-cytokine therapy has been proposed to be a possible treatment for active TAO. We aimed to establish the effects of selected cytokines on intercellular adhesion molecule 1 (ICAM1) expression, glycosaminoglycan (GAG) production and adipogenesis in orbital fibroblasts (OFs) from patients with TAO. Methods: Orbital tissue was taken during surgery from eight patients with TAO and five control subjects. OFs were cultured and ICAM1 expression measured by flow cytometry. GAG production was measured by hyaluronic acid ELISA. OFs were grown in adipogenic media and the degree of adipogenesis quantified. Results: Responses were similar in OFs from patients with and without TAO. Tumour necrosis factor-α (TNFα) and interleukin1 (IL1) (0.1 ng/ml) stimulated ICAM1 expression by eight- to ten-fold. Anti-cytokine agents inhibited the cytokine-upregulated ICAM1 expression by 90–99% (P<0.01). TNFα and IL1 (0.1 ng/ml) increased hyaluronic acid production by 44 and 95% (P<0.01) respectively. Anti-cytokine agents inhibited these responses by 79–138% (P<0.04). TNFα (0.1 ng/ml) inhibited adipogenesis (−0.013 AU and −1.0; P<0.03) whilst IL1 (0.1 ng/ml) stimulated adipogenesis (+0.05 AU and +5.7; P<0.02) measured by oil-red-O extraction and visual assessment respectively. The anti-IL1 agent inhibited IL1-mediated adipogenesis by 69–106% (P<0.04). Conclusion: TNFα and IL1 stimulate ICAM1 expression and GAG production, but have opposite effects on adipogenesis in OFs in vitro. IL1 promotes adipogenesis and its effects can be blocked by anti-IL1 agents in vitro. These agents may be the anti-cytokine treatment of choice for clinical trials in active TAO.

Effects of extracellular pH on tumour necrosis factor-α production by resident alveolar macrophages

2001 ◽  
Vol 101 (3) ◽  
pp. 267-274 ◽  
Author(s):  
Thomas A. HEMING ◽  
Sanat K. DAVÉ ◽  
Divina M. TUAZON ◽  
Ashok K. CHOPRA ◽  
Johnny W. PETERSON ◽  
...  
Keyword(s):  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Inflammatory Responses ◽  
Transcript Abundance ◽  
Extracellular Ph ◽  
Tumour Necrosis Factor Α ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Cellular acid–base status has been found to exert selective actions on the effector functions of activated macrophages (mϕ). We examined the effects of extracellular pH (pHo) on the production of tumour necrosis factor-α (TNF-α) induced by lipopolysaccharide (LPS) in resident alveolar mϕ. Cells were obtained by bronchoalveolar lavage of rabbits, activated in vitro with LPS, and cultured at pHo 5.5, 6.5 or 7.4 for up to 18 h. The relative abundance of TNF-α mRNA peaked at ~ 2 h. The peak transcript abundance was increased at lower pHo values. This finding probably reflected pre-transcription/transcription effects of pH, in as much as the stability of TNF-α mRNA induced with phorbol ester was unaffected by the experimental pHo values. TNF-α secretion by LPS-treated mϕ decreased at lower pHo values. The TNF-α content of mϕ-conditioned media decreased progressively with decrements in pHo. The reduced TNF-α secretion at pHo 5.5 was accompanied by an increase in the cytosolic TNF-α content (compared with that at pHo 7.4), indicating that pHo altered TNF-α secretion due, in part, to the intracellular retention of synthesized cytokine (i.e. a post-translation effect). The data show that pHo has multiple effects (pre-transcription/transcription and post-translation) on TNF-α production induced by LPS in resident alveolar mϕ. These results suggest that the role of alveolar mϕ in inflammatory responses is modulated by pHo, which may be important in tumours/abscesses and sites of infection where the external milieu is acidic.

Παθοφυσιολογία της αντίδρασης του ενδοθηλίου μετά από αγγειοπλαστική νεφρικής αρτηρίας

2014 ◽  
Author(s):  
Κυριακή Ταβερναράκη
Keyword(s):  
Adhesion Molecule ◽  
Intercellular Adhesion Molecule ◽  
Vascular Cell Adhesion ◽  
Intercellular Adhesion Molecule 1 ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Tnf Α ◽  
Factor Α ◽  
Cell Adhesion Molecule 1 ◽  
Necrosis Factor

Σκοπός:Για τη μελέτη του παθοφυσιολογικού μηχανισμού αντίδρασης του τοιχώματος της νεφρικής αρτηρίας που εκλύεται κατά την αγγειοπλαστική με τοποθέτηση stent πραγματοποιήθηκε ποσοτικός προσδιορισμός έξι διαφορετικών παραγόντων φλεγμονής -μεσολαβητών (κυτοκίνες) στον ορό αίματος ασθενών που υποβλήθηκαν σε αυτήν την μέθοδο. Απώτερος σκοπός της μελέτης, μέσω της αξιολόγησης των διαφορών στις συγκεντρώσεις των μεσολαβητών σε ασθενείς που εμφάνισαν ή όχι επαναστένωση του αγγείου, είναι η αναγνώριση καποιού παράγοντα φλεγμονής που θα αποτελέσει δείκτη πρόβλεψης της επαναστένωσης με στόχο την πρόληψη αυτής.Υλικό - Μέθοδος:Μελετήθηκαν είκοσι δύο ασθενείς (17 άνδρες, μέσος όρος ηλικίας 66 έτη), με στένωση στην έκφυση της νεφρικής αρτηρίας και μή καλώς ρυθμιζόμενη υπέρταση, οι οποίοι υποβλήθησαν σε αγγειοπλαστική νεφρικής αρτηρίας με τοποθέτηση stent. Στους ασθενείς αυτούς πραγματοποιήθηκαν αιμοληψίες σε τρεις διαφορετικούς χρόνους: αμέσως πριν την αγγειοπλαστική (baseline), 24 ώρες και 6 μήνες μετά την αγγειοπλαστική και μετρήθηκαν στον ορό τους οι εξής μεσολαβητές: (1) Παράγοντας Νέκρωσης Όγκου-α (Tumor necrosis factor-α, TNF-α), (2) Ιντερλευκίνη 6 (Interleukin-6, IL-6), (3) Πρωτεΐνη χημειοτακτική για τα μονοκύτταρα τύπου-1 (Monocyte Chemoattractant protein-1, MCP-1), (4) Διακυτταρικό μόριο προσκόλλησης-1 (Intercellular adhesion molecule-1, ICAM-1), (5) Μόριο προσκόλλησης αγγειακών κυττάρων-1 (Vascular cell Adhesion Molecule-1, VCAM-1) και (6) Παράγοντας RANTES (Regulated upon Activation Normal T-cell Expressed presumed Secreted). Στους έξι μήνες μετά την αγγειοπλαστική πραγματοποιήθηκε έχρωμο Doppler υπερηχογράφημα και καταγράφηκε η ανάπτυξη ή όχι επαναστένωσης εντός του stent. Επιπλέον, αξιολογήθηκαν οι διαφορές της συγκέντρωσης αυτών σε ασθενείς που εμφάνισαν επαναστένωση της νεφρικής αρτηρίας στους 6 μήνες μετά την αγειοπλαστική συγκριτικά με αυτούς που δεν εμφάνισαν επαναστένωση.Αποτελέσματα:Η συγκέντρωση της ΙL-6 αυξήθηκε σημαντικά 24 ώρες μετά την αγγειοπλαστική (8.3 pg/mL ± 1.24 vs 2.76 pg/mL ± 1.27 τιμές baseline), ενώ στους 6 μήνες μετά επέστρεψε στις προ την επέμβαση τιμές (2.6 pg/mL ± 1.77) (Ρ<.0001). Δεν σημειώθηκαν στατιστικά σημαντικές διαφορές στις συγκεντρώσεις των υπολοίπων μεσολαβητών σε κανέναν από τους τρεις χρόνους. Επίσης, βρέθηκε πως η συγκέντρωση της ΙL-6 τόσο πρίν την αγγειοπλαστική όσο και 6 μήνες μετά την αγγειοπλαστική ήταν σημαντικά υψηλότερη στους ασθενείς που ανάπτυξαν επαναστένωση (8.13 pg/mL ± 4 vs 0.75 pg/mL ± 0.47 [P,.005] και 9.55 pg/ml ± 6.5 vs 0.42 pg/ml ± 0.35 [p<.02] αντίστοιχα).Συμπέρασμα:Με βάση τα αποτελέσματα προτείνουμε πως η αγγειοπλαστική της νεφρικής αρτηρίας με τοποθέτηση stent προκαλεί μια φλεγμονώδη αντίδραση στο τοίχωμα της αρτηρίας, όπως αυτή εκφράζεται με την υψηλή συγκέντρωση ΙL-6 στο αίμα 24 ώρες μετά την επέμβαση. Όσον αφορά στην ανάπτυξη ή όχι επαναστένωσης του αγγείου προτείνουμε πως η ΙL-6 μπορεί να να αναγνωρίσει τους ασθενείς υψηλού κινδύνου και κατ’ επέκταση να αποτελέσει έναν δείκτη πρόβλεψης της επαναστένωσης.

scholarly journals Neutral sphingomyelinase 2 (nSMase2) is the primary neutral sphingomyelinase isoform activated by tumour necrosis factor-α in MCF-7 cells

2011 ◽  
Vol 435 (2) ◽  
pp. 381-390 ◽  
Author(s):  
Christopher J. Clarke ◽  
Emily A. Cloessner ◽  
Patrick L. Roddy ◽  
Yusuf A. Hannun
Keyword(s):  
Tumour Necrosis Factor ◽  
Cell Lines ◽  
Tumour Necrosis ◽  
Tumour Necrosis Factor Α ◽  
Neutral Sphingomyelinase ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor ◽  
Mcf 7

Activation of N-SMase (neutral sphingomyelinase) is an established part of the response of cytokines such as TNF (tumour necrosis factor)-α. However, it remains unclear which of the currently cloned N-SMase isoforms (nSMase1, nSMase2 and nSMase3) are responsible for this activity. In MCF-7 cells, we found that TNF-α induces late, but not early, increases in N-SMase activity, and that nSMase2 is the primary isoform activated, most likely through post-transcriptional mechanisms. Surprisingly, overexpression of tagged or untagged nSMase3 in multiple cell lines had no significant effect on in vitro N-SMase activity. Moreover, only overexpression of nSMase2, but not nSMase1 or nSMase3, had significant effects on cellular sphingolipid levels, increasing ceramide and decreasing sphingomyelin. Additionally, only siRNA (small interfering RNA) knockdown of nSMase1 significantly decreased basal in vitro N-SMase activity of MCF-7 cells, whereas nSMase2 but not nSMase3 siRNA inhibited TNF-α-induced activity. Taken together, these results identify nSMase2 as the major TNF-α-responsive N-SMase in MCF-7 cells. Moreover, the results suggest that nSMase3 may not possess in vitro N-SMase activity and does not affect cellular sphingolipid levels in the cell lines evaluated. On the other hand, nSMase1 contributes to in vitro N-SMase activity, but does not affect cellular sphingolipids much.

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