Respective effects of soluble interleukin-1 receptor and tumour necrosis factor receptor on IL-1 and TNF-α-induced DNA synthesis of common acute lymphoblastic leukaemia blasts in vitro

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.

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Release of tumour necrosis factor alpha into bronchial alveolar lavage fluid following antigen challenge in passively sensitized guinea-pigs

Mediators of Inflammation ◽

10.1155/s0962935192000644 ◽

1992 ◽

Vol 1 (6) ◽

pp. 425-428 ◽

Cited By ~ 2

Author(s):

D. E. Kelly ◽

M. Denis ◽

D. F. Biggs

Keyword(s):

Tumour Necrosis Factor ◽

Guinea Pigs ◽

Tumour Necrosis ◽

Interleukin 1 ◽

Lavage Fluid ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Factor Α ◽

Bronchial Alveolar Lavage ◽

Necrosis Factor

Five groups of ten female guinea-pigs were passively sensitized against ovalbumin (OA) (n = 9) or control guinea-pig serum (n = 1). 24 h later, they received mepyramine (0.5 mg/kg, i.p.) and 30 min later inhaled aerosols of: (A) OA (2 in 0.9% saline, 8 min, n = 4/9); (B) saline (40 min, n = 4/9); (C) LPS (40 min, Escherichia coli 0111:B4, 150 ng/kg in PBS, n = 1/9); and (D) the control animal was treated as in (C) (n = 1). Their tracheas were cannulated under pentobarbital anaesthesia and bronchial alveolar lavage (BAL) was performed with 2 × 5 ml PBS containing BSA (1%) (n = 1 group), or BSA (1%) and aprotinin (1000 KIU/ml) (n = 4 groups), at 30, 60, 90 or 120 min post-inhalations. BAL fluids recovered were centrifuged, the supernatants recovered and frozen until assayed for tumour necrosis factor-α (TNF-α), interleukin-1 (IL-1) and interleukin-6 (IL-6). No TNF-α could be detected unless aprotinin was present in the lavaging solution. BAL fluid from OA-sensitized and control animals that had inhaled LPS contained high levels of TNF-α that peaked at 90 min. BAL fluid from OA sensitized animals that inhaled OA aerosols contained no detectable TNF-α at 30 min, but it was found in increasing amounts at 60, 90 and 120 min; TNF-α was not detected in fluid from any of the animals that inhaled saline. As BAL fluids were toxic to the cells used in the assays, neither IL-1 nor IL-6 could be measured. We conclude that the monokine TNF-α is released into BAL fluid following anaphylactic challenge of passively sensitized guinea-pigs. The presence of the antiprotease, aprotinin, in the lavaging solution is essential for the detection and measurement of TNF-α in BAL fluid.

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Role of tumour necrosis factor receptor-1 and nuclear factor-κB in production of TNF-α-induced pro-inflammatory microparticles in endothelial cells

Thrombosis and Haemostasis ◽

10.1160/th13-11-0975 ◽

2014 ◽

Vol 112 (09) ◽

pp. 580-588 ◽

Cited By ~ 28

Author(s):

Sung Kyul Lee ◽

Seung-Hee Yang ◽

Il Kwon ◽

Ok-Hee Lee ◽

Ji Hoe Heo

Keyword(s):

Endothelial Cells ◽

Tumour Necrosis Factor ◽

Tumour Necrosis ◽

Nuclear Factor Κb ◽

Tumour Necrosis Factor Receptor ◽

Dependent Manner ◽

Nuclear Factor ◽

Tnf Α ◽

Necrosis Factor

SummaryTumour necrosis factor-α (TNF-α) is upregulated in many inflammatory diseases and is also a potent agent for microparticle (MP) generation. Here, we describe an essential role of TNF-α in the production of endothelial cell-derived microparticles (EMPs) in vivo and the function of TNF-α-induced EMPs in endothelial cells. We found that TNF-α rapidly increased blood levels of EMPs in mice. Treatment of human umbilical vein endothelial cells (HUVECs) with TNF-α also induced EMP formation in a time-dependent manner. Silencing of TNF receptor (TNFR)-1 or inhibition of the nuclear factor-κB (NF-κB) in HUVECs impaired the production of TNF-α-induced EMP. Incubation of HUVECs with PKH-67-stained EMPs showed that endothelial cells readily engulfed EMPs, and the engulfed TNF-α-induced EMPs promoted the expression of pro-apoptotic molecules and upregulated intercellular adhesion molecule-1 level on the cell surface, which led to monocyte adhesion. Collectively, our findings indicate that the generation of TNF-α-induced EMPs was mediated by TNFR1 or NF-κB and that EMPs can contribute to apoptosis and inflammation of endothelial cells.

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