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)

To test the hypothesis that the cytokines interleukin-6 (IL-6) and IL-8 may play regulatory roles in the aberrant neovascularization in chronic inflammatory diseases, we examined their effects in a rat sponge model and compared their actions with those of IL-1 and tumor necrosis factor-alpha (TNF-alpha). Daily doses of 3 pmol IL-8, IL-1, TNF-alpha, but not IL-6, significantly accelerated the sponge-induced angiogenesis. Although lower doses (0.3 pmol) of these cytokines were inactive, IL-1 acted synergistically with subthreshold daily doses (10 pmol) of substance P (SP) and bradykinin (BK) to produce an intense angiogenic response. In contrast, IL-8 only interacted positively with IL-1, but not TNF-alpha, SP, or BK. There was no synergism or antagonism between IL-6 and SP. These results demonstrate the discrete interactions between angiogenic factors and cytokines in chronic inflammation and suggest that the sponge model is a good means for the study of such interactions.
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PMID:Interleukin-8 stimulates angiogenesis in rats. 768 27

1. Interleukin-1 beta (IL-1 beta), IL-2 and IL-8 induced a mechanical hyperalgesia following intra-articular (i.artic.) injection into rat knee joints, whereas IL-6 and tumour necrosis factor alpha (TNF-alpha) were without effect. 2. Co-administration of IL-1 receptor antagonist (0.1 micrograms) with IL-1 beta (1 mu), IL-2 (10 mu) or IL-8 (0.1 mu) prevented the subsequent development of the hyperalgesia. 3. Co-administration of desArg9Leu8BK (0.5-5 nmol) with IL-1 beta (1 mu), IL-2 (10 mu) or IL-8 (0.1 mu) reduced the level of hyperalgesia at 1, 4 and 6 h post administration, whereas Hoe 140 (5 pmol) antagonized the hyperalgesia only at the 1 h time point. 4. Intravenous administration of desArg9Leu8BK (10 nmol kg-1) or Hoe 140 (100 pmol kg-1) following IL-1 beta (1 mu), IL-2 (10 mu), or IL-8 (0.1 mu) reversed the subsequent hyperalgesia. 5. Administration of desArg9BK into joints 24 h after pre-treatment with IL-1 beta (1 mu) produced analegsia at low doses (50 pmol) and hyperalgesia at a higher dose (0.5 nmol). Both these effects were blocked by desArg9Leu8BK (0.5 nmol). 6. Administration of desArg9BK (0.5 nmol i.artic.) to animals 24 h after pre-treatment with IL-2 (1-100 mu) or IL-8 (0.1-10 mu) had no effect on the load tolerated by the treated joint. 7. Administration of indomethacin (1 mg kg-1, s.c.) prior to IL-1 beta (1 mu i.artic.) prevented the development of hyperalgesia. Administration of desArg9BK (5 pmol-0.5 nmol, i.artic.) to animals 24 h after indomethacin and IL-1 beta pretreatment had no effect on the load tolerated by the treated joint. 7. Administration of indomethacin (1 mg kg-1, s.c.) prior to IL-1beta (1 u i.artic.) prevented the development of hyperalgesia. Administration of desArg9BK (5 pmol-0.5 nmol, i.artic.) to animals 24 h after indomethacin and IL-1 beta pretreatment had no effect on the load tolerated by the treated joint.8. These data suggest that both bradykinin B1 and B2 receptors are involved in the induction and maintenance of cytokine-induced hyperalgesia. They also show that the induction of B1 receptor-mediated hyperalgesia requires both cyclo-oxygenase products and IL-1 in vivo.
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PMID:The involvement of bradykinin B1 and B2 receptor mechanisms in cytokine-induced mechanical hyperalgesia in the rat. 781 34

1. The hyperalgesic activities in rats of bradykinin, carrageenin and lipopolysaccharide (LPS) were investigated in a model of mechanical hyperalgesia. 2. Bradykinin and carrageenin evoked dose-dependent hyperalgesia with maximum responses of similar magnitude to responses to LPS (1 and 5 micrograms). 3. Hoe 140, an antagonist of BK2 receptors, inhibited in a dose-dependent manner hyperalgesic responses to bradykinin, carrageenin and LPS (1 microgram) but not responses to LPS (5 micrograms), prostaglandin E2, dopamine, tumour necrosis factor alpha (TNF alpha), IL-1, IL-6 and IL-8. 4. Responses to bradykinin and LPS (1 and 5 micrograms) were inhibited by the cyclo-oxygenase inhibitor, indomethacin and by the beta-adrenoceptor antagonist, atenolol. The effects of indomethacin and atenolol were additive: their combination abolished responses to bradykinin and LPS (1 microgram) and markedly attenuated the response to LPS (5 micrograms). 5. Antiserum neutralizing endogenous TNF alpha abolished the response to bradykinin whereas antisera neutralizing endogenous IL-1 beta, IL-6 and IL-8 each partially inhibited the response. The combination of antisera neutralizing endogenous IL-1 beta+IL-8 or IL-6+IL-8 abolished the response to bradykinin. 6. Antisera neutralizing endogenous TNF alpha, IL-1 beta, IL-6 and IL-8 each partially inhibited responses to LPS (1 and 5 micrograms). Increasing the dose of antiserum to TNF alpha or giving a combination of antisera to IL-1 beta+IL-8 or IL-6+IL-8 further inhibited responses to LPS (1 and 5 micrograms). 7. These data show that bradykinin can initiate the cascade of cytokine release that mediates hyperalgesic responses to carrageenin and endotoxin (1 microgram). The lack of effect of Hoe 140 on hyperalgesic responses to LPS (5 microgram) suggests that the release of hyperalgesic cytokines can be initiated independently of bradykinin BK2 receptors.
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PMID:Bradykinin initiates cytokine-mediated inflammatory hyperalgesia. 829 13

Phospholipase C-mediated release of inositol trisphosphate, followed by an increase in free intracellular calcium, is an important signal transduction pathway for several membrane receptors. In the present investigation, the coupling of various receptors to phospholipase C was studied in the human keratinocyte line HaCaT. Inositol trisphosphate formation was determined by anion-exchange chromatography, and the release of intracellular calcium was analysed with the fluorescence probe Fura-2 AM. Activation of HaCaT keratinocytes with bradykinin resulted in a time- and dose-dependent release of inositol trisphosphate and intracellular calcium, with an EC50 value of 50 nM for bradykinin-induced inositol trisphosphate formation. The mediators and cytokines IL-1, IL-4, IL-6, IL-8, EGF and TGF alpha, as well as bombesin, prolactin, carbachol, substance P and retinoic acid, did not activate this pathway. The inability of the mediators examined to activate phospholipase C may be due to lack of the respective cognate receptors or to the use of other signal transduction pathways.
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PMID:Inositol phosphate formation and release of intracellular free calcium by bradykinin in HaCaT keratinocytes. 830 79

Using specific antisera for IL-1 beta and IL-8, as well as cyclooxygenase inhibitors and propranolol, we have demonstrated that these cytokines are responsible for the prostaglandin and sympathetic components of carrageenin-induced hyperalgesia in the rat paw test. The release of IL-1 beta and IL-8 is preceded by the liberation of TNF-alpha. We have also tested in a nociceptive model the effects of bradykinin and a specific bradykinin antagonist, HOE 140, on the hyperalgesia induced by carrageenin and lipopolysaccharide (LPS). Bradykinin-induced hyperalgesia was abolished by HOE 140 and by treatment of the paws with anti-TNF-alpha antisera. HOE 140 significantly inhibited the hyperalgesia induced by carrageenin and LPS. It is suggested that in these two models bradykinin is associated with the release of hyperalgesic cytokines.
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PMID:Bradykinin release of TNF-alpha plays a key role in the development of inflammatory hyperalgesia. 831 26

The involvement of bradykinin (BK) B1 and B2 receptors in cytokine-induced hyperalgesia has been studied in the rat. Intraplantar injections of interleukin (IL) 1 beta and tumor necrosis factor alpha (TNF alpha) induced thermal hyperalgesia, with in the the case of IL-1 beta, contralateral hyperalgesia also present. Subsequent to administration of IL-1 beta, but not after TNF alpha, des-Arg9-BK reduced the withdrawal latency in both ipsi- and contra-lateral paws. Mechanical hyperalgesia was also induced by IL-1 beta, IL-2, and IL-8 when injected into rat knee joints, whereas IL-6 and TNF alpha were without effect. Coadministration of des-Arg9,Leu8-BK prevented the development of the cytokine-induced hyperalgesia for the duration of the experiment (6 h), but HOE-140 only reversed the hyperalgesia for the 1st h. At 3.5 h after IL-1 beta, IL-2, or IL-8, administration of des-Arg9,Leu8-BK or HOE-140 (iv) completely reversed the hyperalgesia. Twenty-four hours after pretreatment with IL-1 beta, injection of des-Arg9-BK into the joint produced opposite effects, depending on the dose: at 50 pmol the hyperalgesia was reversed, but at 0.5 nmol there was further hyperalgesia. Both responses were blocked by B1 but not B2 receptor antagonists. These data suggest that both B1 and B2 receptors are involved in the induction and maintenance of cytokine-induced hyperalgesia. B1 receptors appear to play a more important role than B2 receptors in the development of mechanical hyperalgesia.
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PMID:Bradykinin B1 and B2 receptor mechanisms and cytokine-induced hyperalgesia in the rat. 884 17

Cytokines are known to participate in the process of parturition within a paracrine network in fetal membranes. Bradykinin can also contribute to this process, increasing the release of eicosanoids from decidua cells. In this study, we present evidence for a cross-link between bradykinin and the cytokines. Short and long term cultures of human decidua cells were incubated for 4 h and 24 h with and without bradykinin. IL-6 and IL-8 were determined in the supernatants by ELISA. Results show a large interindividual variability in the basal secretion of IL-6 and IL-8 and a clear increase in the secretion of both ILs in response to bradykinin. By this amplifying effect on cytokine secretion, bradykinin can initiate local and systemic effects of amniochorionitis.
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PMID:Bradykinin stimulates interleukin-6 and interleukin-8 secretion of human decidua derived cells. 914 88

G protein-coupled receptors transduce the signal of a wide variety of hormones, neurotransmitters, cytokines, and other molecules across the cell membrane to elicit the corresponding response inside the target cells. We describe in this paper the molecular cloning and tissue distribution of a novel rat G protein-coupled receptor, GPR41, with highest homology to the human orphan G protein-coupled receptor DRY12. A lower degree of homology was seen with the receptors for bradykinin, angiotensin, and IL8. The expression of GPR41 appears to be the highest in brain and lung tissues, with lesser expression in heart, skeletal muscle, and kidney, as assayed by northern blotting. No GPR41 message was seen in spleen, liver, or testes. GPR41 failed to bind any of the ligands tested.
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PMID:Molecular cloning and tissue expression of a novel orphan G protein-coupled receptor from rat lung. 916 87

1. We recently demonstrated the presence of phospholipase C-coupled bradykinin (BK) B2-receptors in human primary and SV40 virus-immortalized corneal epithelial (CEPI) cells. 2. The aims of the present studies were to demonstrate the specific binding of [3H]-BK to CEPI cell membranes and to study its pharmacological characteristics. In addition, we wished to study the functional coupling of the BK receptors to various physiological and pathological mechanisms in the CEPI cells, including phosphoinositide (PI) turnover, intracellular Ca2+-mobilization ([Ca2+]i), cell proliferation (via [3H]-thymidine incorporation), and the release of various cytokines, collagenase-1 (matrix metalloproteinase-1) and prostaglandin E2 (PGE2). 3. Specific [3H]-BK binding comprised 83 +/- 2% of the total binding, and was of high affinity (Kd = 1.66 +/- 0.52 nM, n = 5), saturable (Bmax = 640 +/- 154 fmol g(-1) wet weight) and reversible. Competition studies yielded the following affinity values for BK and a number of BK-related peptides: Hoe-140 (D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]BK; icatibant): Ki = 0.17 +/- 0.07 nM; BK: Ki = 1.0 +/- 0.11 nM; [Tyr8]-BK: Ki = 12.9 +/- 2.3 nM; [des-Arg9]-BK: Ki > 9,200 nM (all n = 3-5)). 4. BK potently stimulated PI turnover (EC50 = 2.3 +/- 0.3 nM; n = 7) and [Ca2+]i mobilization (EC50 = 8-20 nM) in CEPI cells and both responses were inhibited in a concentration-dependent manner by 100 nM-10 microM Hoe-140, a selective B2-receptor antagonist, and also inhibited by the selective phospholipase C (PLC) inhibitor, U73122 (1-(6-((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1 H-pyrrole-2,5-dione) (IC50 = 3.0 +/- 1.6 microM). BK-induced [Ca2+]i mobilization was reduced by about 30% in the presence of 4 mM EGTA, but was not significantly affected by 100 nM nifedipine. 5. BK (0.1 nM-10 microM) significantly (P<0.05-0.001) stimulated [3H]-thymidine incorporation into CEPI cellular DNA. However, while interleukin-1alpha (IL-1alpha; 10 ng ml(-1)) potently stimulated the release of IL-6, IL-8 and granulocyte macrophage colony-stimulating factor from CEPI cells, BK (0.1 nM-10 microM) was without effect. 6. Whilst phorbol-12-myristate-13-acetate (PMA; 3 microg ml(-1)) and 10% foetal bovine serum (positive control agents) significantly stimulated the release of both MMP-1 and PGE2 from CEPI cells, BK (0.1 nM-10 microM) was without any significant effect under these conditions. 7. In conclusion, these data indicate that the CEPI cells express high-affinity [3H]-BK binding sites representing B2-subtype BK receptors coupled to PI turnover and [Ca2+]i mobilization which appear to stimulate [3H]-thymidine incorporation into cellular DNA. In contrast, BK failed to elicit the release of PGE2, various cytokines and MMP-1 from CEPI cells. These results suggest that BK may have a potential role in corneal epithelium wound healing by stimulating cell proliferation.
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PMID:Effects of bradykinin on signal transduction, cell proliferation, and cytokine, prostaglandin E2 and collagenase-1 release from human corneal epithelial cells. 955 96

IL-8 is an important neutrophil and eosinophil chemoattractant in asthma. A recent report has suggested that bradykinin (BK), an asthmatic mediator, induces the release of IL-8 in nonairway cells. We have recently reported that BK causes cyclooxygenase (COX)-2 induction and PGE2 release in human airway smooth muscle (ASM) cells. In this study, we tested the ability of BK to induce IL-8 from these cells and explored the role of COX products and COX-2 induction in this process. Confluent serum-deprived human ASM cells were studied. IL-8 was assayed by specific ELISA. Unstimulated cells released low levels of IL-8. BK enhanced IL-8 release in a concentration- and time-dependent fashion (maximum 50-fold increase over basal). The nonselective COX inhibitor indomethacin and the selective COX-2 inhibitor NS-398 strongly inhibited BK-stimulated PGE2 and IL-8 production. The COX substrate arachidonic acid also caused PGE2 and IL-8 production, and its effect was inhibited by nonselective COX inhibitors but unaffected by NS-398. Both the BK- and arachidonic acid-induced IL-8 production was inhibited by the protein synthesis inhibitors cycloheximide and actinomycin D and by the steroid dexamethasone. Furthermore, exogenous PGE2 and calcium ionophore A23187 also stimulated IL-8 release. BK-induced IL-8 release was mimicked by the BK B2 receptor agonist (Tyr(Me)8)-BK and was potently inhibited by the selective B2 receptor antagonist HOE-140. These results suggest that human ASM can be a source of IL-8 and also that endogenous prostanoids, involving both COX-1 and COX-2, have a novel role in mediating BK-induced IL-8 production.
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PMID:Bradykinin stimulates IL-8 production in cultured human airway smooth muscle cells: role of cyclooxygenase products. 972 50


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