Interleukin-1 beta and tumor necrosis factor-alpha synergistically stimulate nerve growth factor synthesis in rat mesangial cells

1991 ◽  
Vol 261 (5) ◽  
pp. F792-F798 ◽  
Author(s):  
P. Steiner ◽  
J. Pfeilschifter ◽  
C. Boeckh ◽  
H. Radeke ◽  
U. Otten
Keyword(s):  
Gene Expression ◽  
Nerve Growth Factor ◽  
Tumor Necrosis ◽  
Mesangial Cells ◽  
Interleukin 1 ◽  
Tnf Alpha ◽  
Interleukin 1 Beta ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

Recent evidence indicates that cytokines are potent inducers of nerve growth factor (NGF) expression both in peripheral tissues and the central nervous system and that NGF, in addition to its neurotrophic action, also acts as an immunoregulatory agent. It was of interest to investigate whether inflammatory cytokines affect NGF production in renal mesangial cells, which play a crucial role in the modulation of the local immune function in the glomerulus. Our results show that the simultaneous addition of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) elicited a marked (13-fold) increase of NGF protein released by cultured rat glomerular mesangial cells within 24 h, whereas IL-1 alpha in combination with TNF-alpha, as well as the cytokines alone, did not promote the synthesis of NGF. The synergistic effect was dose dependent (maximal at 1 nM) and due to enhanced gene expression, since the cytokine treatment caused a fivefold increase in NGF mRNA after 8 h. Stimulation of NGF synthesis was abolished by mepacrine and dexamethasone, indicating that phospholipase A2 may be involved in NGF regulation. Moreover, pretreatment of the cells with the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) abolished induction of NGF by cytokines; in contrast, the specific cyclooxygenase inhibitors indomethacin and diclofenac failed to modify NGF production. These data suggest that a lipoxygenase metabolite produced in response to IL-1 beta and TNF-alpha acts as a mediator in NGF gene expression. In conclusion, these findings support a model in which a cytokine cascade including NGF may play an important role in the pathophysiology of inflammatory renal diseases.

Interleukin-1 beta and tumor necrosis factor-alpha synergistically induce NO synthase in rat vascular smooth muscle cells

1994 ◽  
Vol 266 (4) ◽  
pp. R1197-R1203 ◽  
Author(s):  
D. Beasley ◽  
M. Eldridge
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Tumor Necrosis ◽  
Interleukin 1 ◽  
No Synthase ◽  
Tnf Alpha ◽  
Interleukin 1 Beta ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

Cytokine-inducible nitric oxide (NO) production has been implicated in the pathogenesis of septic shock. The present study was designed to determine which cytokines induce expression of the NO synthase gene in rat aortic vascular smooth muscle cells (VSMC) in vitro and whether NO synthase gene expression is inducible in vivo. NO synthase mRNA appeared after 4-h exposure to interleukin-1 beta (IL-1 beta), and levels continued to increase up to 24 h. Levels of NO synthase transcripts were greatest in VSMC treated with IL-1 beta (1 nM), lower in VSMC treated with Escherichia coli lipopolysaccharide (LPS; 100 micrograms/ml), and just detectable in VSMC treated with tumor necrosis factor-alpha (TNF-alpha; 1 nM). IL-1 beta, TNF-alpha, and LPS each induced NO synthase activity, assessed by release of nitrite, conversion of L-arginine to L-citrulline, and increased levels of guanosine 3',5'-cyclic monophosphate, whereas IL-2, IL-6, and interferon-gamma were ineffective. IL-1 beta was more potent and effective than TNF-alpha; however, submaximal concentrations of TNF-alpha acted synergistically with IL-1 beta to induce NO synthase gene expression and activity. Inducible NO synthase mRNA was present in aorta from rats 6 h after treatment with LPS (5 mg/kg), but not at 24 h. Synergistic activation of NO synthase gene expression in VSMC by IL-1 beta and TNF-alpha may contribute to hypotension in sepsis.

scholarly journals Keratinocyte growth factor, tumor necrosis factor-alpha and interleukin-1 beta gene expression in cultured fibroblasts and keratinocytes from burned patients

2013 ◽  
Vol 28 (8) ◽  
pp. 551-558 ◽  
Author(s):  
Alfredo Gragnani ◽  
Bruno Rafael Müller ◽  
Ismael Dale Contrim Guerreiro da Silva ◽  
Samuel Marcos Ribeiro de Noronha ◽  
Lydia Masako Ferreira
Keyword(s):  
Gene Expression ◽  
Tumor Necrosis ◽  
Keratinocyte Growth Factor ◽  
Interleukin 1 ◽  
Interleukin 1 Beta ◽  
Necrosis Factor Alpha ◽  
Cultured Fibroblasts ◽  
Factor Alpha ◽  
Beta Gene ◽  
Necrosis Factor

Colchicine has opposite effects on interleukin-1 beta and tumor necrosis factor-alpha production

1991 ◽  
Vol 261 (4) ◽  
pp. L315-L321 ◽  
Author(s):  
J. N. Allen ◽  
D. J. Herzyk ◽  
M. D. Wewers
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Cytokine Production ◽  
Interleukin 1 ◽  
Tnf Alpha ◽  
Mrna Levels ◽  
Interleukin 1 Beta ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

To study the role of microtubules in cytokine production, the effect of the microtubule depolymerizing agent colchicine on lipopolysaccharide endotoxin (LPS)-induced interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) release by blood monocytes and alveolar macrophages were examined. Immunofluorescence microscopy demonstrated that LPS resulted in the appearance of microtubule-containing cytoplasmic appendages and that colchicine, which resulted in microtubule disruption in monocytes, blocked appendage formation. Colchicine resulted in approximately 50% increase in LPS-induced IL-1 beta release and a 50% decrease in LPS-induced TNF-alpha release by human monocytes at all doses of LPS tested. Although colchicine resulted in a statistically significant increase in LPS-stimulated human alveolar macrophage IL-1 beta release, the increase was not as great as that observed with monocytes. Northern blot analysis suggested that the colchicine effect occurs pretranslationally because colchicine caused an increase in LPS-stimulated IL-1 beta mRNA levels and a decrease in TNF-alpha mRNA levels. These results suggest that microtubules contribute to the regulation of endotoxin-stimulated mononuclear phagocyte cytokine production and that this regulation differs significantly between IL-1 beta and TNF-alpha.

scholarly journals Effects of Naked Gold Nanoparticles on Proinflammatory Cytokines mRNA Expression in Rat Liver and Kidney

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Haseeb A. Khan ◽  
Mohamed Anwar K. Abdelhalim ◽  
Abdullah S. Alhomida ◽  
Mohammed S. Al-Ayed
Keyword(s):  
Gene Expression ◽  
Gold Nanoparticles ◽  
Proinflammatory Cytokines ◽  
Tumor Necrosis ◽  
Interleukin 1 ◽  
Interleukin 1 Beta ◽  
Necrosis Factor Alpha ◽  
Liver And Kidney ◽  
Factor Alpha ◽  
Necrosis Factor

The data on the biocompatibility of naked gold nanoparticles (GNPs) are scarce, and their interpretation is controversial. We studied the acute (1 day) and subchronic (5 days) effects of GNPs (10 and 50 nm diameter) on expression of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) in the liver and kidneys of rats. In the liver, the GNPs of both sizes (10 and 50 nm) significantly increased the cytokines gene expression on day 1 which was subsided on day 5; the GNPs of 50 nm size produced more severe inflammatory response as compared to smaller sized GNPs. In the kidney, the GNPs did not produce any significant change in the expression of IL-1β. Although the gene expression of IL-6 and TNF-αwas not affected by GNPs of 10 nm size, 50 nm GNPs significantly increased the expression of IL-6 and TNF-αin the kidneys of rats on day 1 after treatment which returned to normalcy on day 5. These findings indicate the possible immunocompatibility of medium sized GNPs as they caused only a transient acute phase increase in proinflammatory cytokines expression followed by their normalcy during the repeated exposure.

scholarly journals Tumor necrosis factor alpha/cachectin and interleukin 1 beta initiate meningeal inflammation.

1990 ◽  
Vol 172 (2) ◽  
pp. 497-507 ◽  
Author(s):  
O Ramilo ◽  
X Sáez-Llorens ◽  
J Mertsola ◽  
H Jafari ◽  
K D Olsen ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Inflammatory Response ◽  
Tumor Necrosis ◽  
Interleukin 1 ◽  
Tnf Alpha ◽  
Interleukin 1 Beta ◽  
Necrosis Factor Alpha ◽  
Meningeal Inflammation ◽  
Factor Alpha ◽  
Necrosis Factor

Although previous studies using human cytokines in rabbits and rats have provided evidence of the participation of tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) in the meningeal inflammatory cascade, the results obtained by several groups of investigators have been discordant or, at times, contradictory. In the present study, homologous cytokines were applied to the rabbit meningitis model. Intracisternal administration of 10(2)-10(5) IU of purified rabbit TNF-alpha (RaTNF-alpha) produced significant cerebrospinal fluid (CSF) inflammation. A similar response was observed after intracisternal inoculation of 5-200 ng of rabbit recombinant IL-1 beta (rrIL-1 beta). Preincubation of these two mediators with their specific antibodies resulted in an almost complete suppression of the CSF inflammatory response. In animals with Haemophilus influenzae type b lipooligosaccharide-induced meningitis, intracisternal administration of anti-rrIL-1 beta, anti-RaTNF-alpha, or both resulted in a significant modulation of meningeal inflammation. Simultaneous administration of 10(3) IU of RaTNF-alpha and 5 ng of rrIL-1 beta resulted in a synergistic inflammatory response manifested by a more rapid and significantly increased influx of white blood cells into the CSF compared with results after each cytokine given alone. These data provide evidence for a seminal role of TNF-alpha and IL-1 beta in the initial events of meningeal inflammation.

NF-IL6 and AP-1 cooperatively modulate the activation of the TSG-6 gene by tumor necrosis factor alpha and interleukin-1

1994 ◽  
Vol 14 (10) ◽  
pp. 6561-6569
Author(s):  
L Klampfer ◽  
T H Lee ◽  
W Hsu ◽  
J Vilcek ◽  
S Chen-Kiang
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Interleukin 1 ◽  
Human Fibroblasts ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Normal Human ◽  
Factor Alpha ◽  
Necrosis Factor

Tumor necrosis factor alpha (TNF-alpha) and interleukin-1 (IL-1) activate transcription of the TSG-6 gene in normal human fibroblasts through a promoter region (-165 to -58) that encompasses an AP-1 and a NF-IL6 site. We show by deletion analysis and substitution mutagenesis that both sites are necessary for activation by TNF-alpha. Activation by IL-1 requires the NF-IL6 site and is enhanced by the AP-1 site. These results suggest that the NF-IL6 and AP-1 family transcription factors functionally cooperate to mediate TNF-alpha and IL-1 signals. Consistent with this possibility, IL-1 and TNF-alpha markedly increase the binding of Fos and Jun to the AP-1 site, and NF-IL6 activates the native TSG-6 promoter. Activation by NF-IL6 requires an intact NF-IL6 site and is modulated by the ratio of activator to inhibitor NF-IL6 isoforms that are translated from different in-frame AUGs. However, the inhibitor isoform can also bind to the AP-1 site and repress AP-1 site-mediated transcription. The finding that the inhibitor isoform antagonizes activation of the native TSG-6 promoter by IL-1 and TNF-alpha suggests that NF-IL6 has a physiologic role in these cytokine responses. Thus, the functionally distinct NF-IL6 isoforms cooperate with Fos and Jun to positively and negatively regulate the native TSG-6 promoter by TNF-alpha and IL-1.

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