Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study analyzes the effects of the T cell cytokines IL-4 and IFN-gamma on the spontaneous and stimulated production of IL-8, MCP-1, IL-1 receptor antagonist (IL-1ra), and PGE by synoviocytes from rheumatoid arthritis (RA) and osteoarthritis (OA) patients. Cells from both sources constitutively released IL-8 and MCP-1, but no IL-1ra or PGE. Stimulation with IL-1 beta or TNF-alpha massively increased chemokine production and induced the generation of PGE and low amounts of IL-1ra. The constitutive or cytokine-stimulated release of IL-8 was inhibited by IFN-gamma, but not by IL-4. The constitutive or IL-1 beta-stimulated release of MCP-1, by contrast, was markedly enhanced by IL-4 and IFN-gamma. Both cytokines, however, had only borderline effects on the release stimulated by TNF-alpha. The yield of IL-1ra was strongly enhanced by IFN-gamma in all cases, whereas the effect of IL-4 was pronounced only in IL-1 beta-stimulated OA synoviocytes. IL-4, on the other hand, markedly decreased the release of PGE, which was less susceptible to IFN-gamma. The observed effects on chemokines, IL-1ra expression, and PGE release by synoviocytes suggest that IFN-gamma and IL-4 are important regulatory elements in the inflamed synovium and may exert anti-inflammatory effects.
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PMID:Production of interleukin-1 receptor antagonist, inflammatory chemotactic proteins, and prostaglandin E by rheumatoid and osteoarthritic synoviocytes--regulation by IFN-gamma and IL-4. 812 Apr 7

Bone marrow stromal cells regulate marrow haematopoiesis by secreting interleukins (IL) such as IL-8. Lipid mediators modulate IL-8 synthesis in numerous cell types. We have investigated the effects of 5 lipid mediators (PAF, PGE(2), LTB(4), 12-HETE and 15-HETE) on the spontaneous and cytokine-induced IL-8 synthesis by human bone marrow stromal cells. By using reverse-transcriptase polymerase chain reaction (RT-PCR) we demonstrate that these cells constitutively express IL-8 transcripts. By using a specific ELISA, we found that the production of IL-8 by marrow stromal cells is enhanced after stimulation with 12-HETE (1 microM) both in serum-free and serum-containing culture medium. LTB(4)(1 microM) enhances IL-8 production only in serum-supplemented medium. PAF, PGE(2)and 15-HETE (1 microM to 0.1 nM) have no effect on the spontaneous and serum-induced production of IL-8 by human bone marrow stromal cells. PGE(2)(1 microM or 10 nM) reduces marrow stromal cell IL-8 synthesis in response to IL-1alpha or TNF-alpha. In contrast, PAF, 12-HETE, 15-HETE and LTB(4)have no effect. In conclusion, various lipid mediators modulate the spontaneous, serum- or cytokine-induced IL-8 synthesis by bone marrow stromal cells, highlighting, for the first time, their potential role in the regulation of IL-8 production within the human bone marrow.
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PMID:Lipid mediators modulate the synthesis of interleukin 8 by human bone marrow stromal cells. 1043 8

We have proposed that exposure of epithelial cell membrane lipids in the lung (mainly phospholipids) to ozone will generate lipid ozonation products (LOP), which could be responsible for the proinflammatory effects of ozone. The ozonation of phosphocholine, the principal membrane phospholipid, produces a limited number of LOP, including hydroxyhydroperoxides and aldehydes. We now report that exposure of cultured human bronchial epithelial cells to the ozonized 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) product, 1-palmitoyl-2-(9-oxononanoyl)-sn-glycero-3-phosphocholine (PC-ALD), a phospholipase A(2) (PLA(2))-stimulatory LOP, resulted in a 113 +/- 11% increase in the amounts of tritiated platelet-activating factor ((3)H-PAF) released apically. (3)H-PAF release was also induced by 1-hydroxy-1-hydroperoxynonane of ozonized POPC (HHP-C9), a phospholipase C (PLC)- stimulatory LOP (134 +/- 40% increase in (3)H-PAF). PC-ALD at 10 microM, but not HHP-C9, induced a 127 +/- 24% increase in prostaglandin E(2) (PGE(2)) release (n = 6, p < 0.05). In contrast, HHP-C9, but not PC-ALD, induced interleukin (IL)-6 release (178 +/- 23% increase, n = 6, p < 0.05) and IL-8 release (101 +/- 23% increase, n = 8, p < 0. 05). These results suggest that LOP-dependent release of proinflammatory mediators may play an important role in the early inflammatory response seen during exposure to ozone.
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PMID:Induction of inflammatory mediators in human airway epithelial cells by lipid ozonation products. 1058 9

Tumour necrosis factor alpha (TNF-alpha) inflammatory activity is mediated, at least in part, by prostaglandin E(2)(PGE(2)). In osteoarthritis (OA), other cytokines are believed to play a role by interacting with TNF-alpha. Using OA synovial fibroblasts, we investigated the effects of interleukin 8 (IL-8), leukaemia inhibitory factor (LIF) and IL-11 on the level of TNF-alpha-induced PGE(2), and their impact on the TNF-alpha-induced cellular signalling cascades including the TNF-receptor (TNF-R), soluble TNF-R (TNF-sR), cytoplasmic phospholipase A2 (cPLA2), cyclooxygenase 2 (COX-2), and the transcription factors NF-kappaB, C/EBP, CREB and AP-1.IL-8 increased in a synergistic manner (282% at 5 ng/ml) and LIF in an additive fashion (69% at 50 ng/ml) the TNF-alpha-induced PGE(2)release, while IL-11 reduced it (52% at 5 ng/ml). IL-8 (5 ng/ml) and LIF (50 ng/ml) alone upregulated (30%) the TNF-R binding level, but significantly downregulated the TNF-alpha-induced levels (P<0.007 and P<0.004, respectively) and the TNF-sR55 level. In contrast, IL-11 reduced the basal level by 18% (P<0.005) and the TNF-alpha-induced level of TNF-R by 51% (P<0.01) as well as decreasing both TNF-sR55 and TNF-sR75. The COX-2 synthesis level was increased by IL-8 and LIF under TNF-alpha treatment but downregulated by IL-11. IL-8 and LIF either alone or under TNF-alpha treatment increased the cPLA2 synthesis, while IL-11 decreased the level under both conditions. Interestingly, IL-8 induced in a synergistic manner and LIF in an additive fashion, the level of cPLA2 activity. IL-8 and LIF had no effect on the TNF-alpha-induced NF-kappaB accumulation, while IL-11 significantly decreased it (P<0. 02). All three cytokines inhibited TNF-alpha-induced C/EBP, but no true effect was noted for AP-1 and CREB in the presence of TNF-alpha. These results indicate that IL-8 synergizes and LIF potentiates the TNF-alpha PGE(2)effect which appears to be mediated mostly by increasing cPLA2 activity level. On the other hand, IL-11 alone had no effect on the PGE(2)release, but in conjunction with TNF-alpha, this cytokine showed anti-inflammatory properties. This study provides a rational foundation to develop therapeutic strategies for the treatment of OA by shedding light on the mechanisms of action of three prominent cytokines at work in articular joint tissues.
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PMID:Differential effects of IL-8, LIF (pro-inflammatory) and IL-11 (anti-inflammatory) on TNF-alpha-induced PGE(2)release and on signalling pathways in human OA synovial fibroblasts. 1062 27

The effects of five inflammatory cytokines, i.e. interleukin(IL)-1alpha, IL-1beta, IL-6, IL-8 and tumor necrosis factor-alpha (TNF-alpha) on prostaglandin E(2) (PGE(2)) production from amnion cells cultured in a serum-free condition was evaluated. After human amnion cells obtained from term placenta were incubated with the inflammatory cytokines at various concentrations, PGE(2) production in the culture supernatant was determined using an enzyme immunoassay method. Under a serum-free culture condition, an increase in PGE(2) production by IL-1alpha and IL-1beta was observed at concentrations of 10 and 100 ng/ml compared to control cultures. However, the increases in PGE(2) production by IL-6 and IL-8 were found at relatively high concentrations, i.e. at 100 and 200 ng/ml. TNF-alpha induced a significant increase in PGE(2) production at 50 and 100 ng/ml, but not at 200 ng/ml. These data suggest that these inflammatory cytokines directly stimulate PGE(2) production from amnion cells and may initiate premature labor if amniotic inflammatory cytokines are elevated, e.g. following intrauterine infection.
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PMID:Effects of inflammatory cytokines on prostaglandin E(2) production from human amnion cells cultured in serum-free condition. 1067 14

IL-18 shares with IL-1 the same family of receptors and several identical signal transduction pathways. Because of these similarities, IL-18 was investigated for its ability to induce prostaglandin E(2) (PGE(2)) synthesis in human peripheral blood mononuclear cells (PBMC), a prominent, proinflammatory property of IL-1. IL-18 was highly active in PBMC by inducing the synthesis of the chemokine IL-8; however, no induction of PGE(2) synthesis nor cyclooxygenase type-2 gene expression was observed in PBMC stimulated with IL-18. In the same cultures, IL-1beta induced a 12-fold increase in PGE(2). Although IL-1beta-induced IL-8 synthesis was augmented 3-fold by IL-18, IL-18 suppressed IL-1beta-induced PGE(2) production by 40%. The suppressive effect of IL-18 on PGE(2) production was mediated by interferon (IFN)-gamma because anti-human IFN-gamma-antibody prevented IL-18-induced reduction in PGE(2). Consistent with these observations, IL-12, a known inducer of IFN-gamma, augmented IL-1beta-induced IFN-gamma but suppressed IL-1beta-induced PGE(2) by 75%. IL-18 binding protein (IL-18BP) is a naturally occurring and specific inhibitor of IL-18. When recombinant IL-18BP was added to PBMC cultures, unexpectedly, spontaneous PGE(2) production increased. PGE(2) production was also increased by the addition of IL-18BP to PBMC stimulated with either IL-1beta or IL-12 and also in whole blood cultures stimulated with Staphylococcus epidermidis. These studies demonstrate that IL-18BP decreases endogenous IL-18 activity by reducing IFN-gamma-mediated responses.
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PMID:IL-18 binding protein increases spontaneous and IL-1-induced prostaglandin production via inhibition of IFN-gamma. 1068 39

There is a growing appreciation of the importance of activin as a modulator of immune function. The aim of the present study was to determine whether activin A exerts any effects on cytokine and prostaglandin (PG) production by the tissues of pregnancy. Explant cultures were established for amnion, choriodecidual and placental tissues derived from pregnancies delivered at term by Caesarean section (n=5 placentae). Explants were treated with activin A (0.5, 5 and 50 ng/ml) in serum-free Ham's F12/DME media for 24 h (n=3-4 replicates). Production rates of interleukin (IL)-1beta, IL-6, IL-8, tumour necrosis factor-alpha (TNF-alpha) and PGE(2)were determined using immunoassay. Differences between treatment groups were analysed by ANOVA followed by Dunnett's test;P< 0.05 was considered to be significant. Amnion IL-6 production exhibited biphasic responses to activin A: at 5 ng/ml activin A, IL-6 production was significantly stimulated (to 246+/-74.6 per cent of control (mean+/-sem), while at 50 ng/ml it was significantly inhibited (to 46+/-7.4 per cent of control). IL-8 and PGE(2)production by amnion showed significant responses to activin A that were similar to those of IL-6. No significant effects of activin A were observed on choriodecidual and placental IL-6, IL-8 and PGE(2)production. However, TNF-alpha production was significantly inhibited by 50 ng/ml activin A in both choriodecidual and placental explants (to 43+/-9.7 per cent and 51+/-6.7 per cent of control, respectively). Placental IL-1beta production was not altered by treatment with activin A at any concentration. These findings support the concept of activin as an immune modulator in tissues of pregnancy.
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PMID:Activin A exerts both pro- and anti-inflammatory effects on human term gestational tissues. 1069 49

We have recently shown that endogenous prostanoids are critical in bradykinin-stimulated interleukin (IL)-8 release from human airway smooth muscle (ASM) cells. In this study, we tested the ability of transforming growth factor (TGF)-beta1 to stimulate IL-8 release, cyclooxygenase (COX)-2 expression and PGE(2) generation in cultured human ASM cells and explored the role of COX products and COX-2 induction on IL-8 release. TGF-beta1 stimulated IL-8 release, COX-2 induction, and PGE(2) generation in a concentration- and time-dependent manner. Maximal IL-8 release was achieved with 10 ng/ml of TGF-beta1 after 16 h of incubation, which was inhibited by the transcription inhibitor actinomycin D and the corticosteroid dexamethasone but was not affected by the nonselective COX inhibitor indomethacin and the selective COX-2 inhibitor NS-398 despite their inhibition on TGF-beta1-induced PGE(2) release. These results show for the first time that TGF-beta1 stimulates IL-8 release, COX-2 induction, and PGE(2) generation in human ASM cells and that PGE(2) generation is not critical for TGF-beta1-induced IL-8 release. These findings suggest that TGF-beta1 may play an important role in the pathophysiology of asthma.
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PMID:TGF-beta1 stimulates IL-8 release, COX-2 expression, and PGE(2) release in human airway smooth muscle cells. 1089 19

1. The effect of IL-1ra on response to intraplantar (i.pl.) injection of LPS, carrageenin, bradykinin, TNFalpha, IL-1beta, IL-8, PGE(2) and dopamine was investigated in a model of mechanical hyperalgesia in rats. 2. IL-1ra inhibited hyperalgesic response to LPS, carrageenin, bradykinin, TNFalpha, and IL-1beta, but not responses to IL-8, PGE(2) and dopamine. 3. A sheep anti-rat IL-1ra serum potentiated response to LPS, carrageenin, bradykinin, TNFalpha and IL-1beta but not IL-8. 4. Carrageenin and LPS stimulated and production of immunoreactive TNFalpha, IL-1beta and IL-1ra in the skin of injected paws. 5. The inhibition by IL-1ra of the hyperalgesic response to carrageenin was not affected by antibodies neutralizing IL-4 and IL-10. 6. In mice, IL-1ra inhibited the nociceptive response to i.p. injection of acetic acid. 7. These data suggest that IL-1ra, released at sites of inflammation, limits inflammatory hyperalgesia. This effect is independent of (IL-1ra-induced) IL-4 and IL-10 and appears to be the result of antagonism by IL-1ra of IL-1beta-stimulated eicosanoid production.
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PMID:Cytokine-mediated inflammatory hyperalgesia limited by interleukin-1 receptor antagonist. 1090 85

High levels of prostaglandins are produced in human oropharyngeal carcinoma (OPC). Five human OPC cell lines tested expressed both isoforms of cyclooxygenases (COX). The pan-COX inhibitor ketorolac continuously and significantly decreased PGE(2) production and IL-6 and IL-8 levels in all OPC cell lines tested, but did not affect IL-1alpha, GM-CSF levels, or in vitro tumor cell growth. In contrast, ketorolac reduced OPC growth in vivo. The OPC cell lines used express the IL-6 receptor, and IL-6 stimulation of these cells causes transduction to occur via STAT3 pathway activation. Coincubation with OPC cell lines with conditioned medium from a TPA-exposed HL-60 cells stimulated growth proportional to the IL-6 levels measured in the conditioned medium. This growth effect was specifically inhibited by anti-IL-6 antibody. These results are consistent with cytokine products of inflammatory cells having paracrine growth effects on OPC. If chronic inflammation plays a role in promoting the development of OPC, this mechanism may also apply to other epithelial tumor systems modulated by COX activity.
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PMID:Cyclooxygenase regulates human oropharyngeal carcinomas via the proinflammatory cytokine IL-6: a general role for inflammation? 1092 84


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