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)

The goal of this study was to design a model system for the assessment of phototoxic potential using a human reconstructed epidermis (HRE, SkinEthic Laboratories, Nice, France), by testing some representative phototoxic (P) and non-phototoxic (NP) compounds and finished topical products. The tissue response to 24-h application of 5-5000 microg/mL of the test agents in the presence and absence of UVA light was analyzed in terms of viability (Lactate Dehydrogenase release), pro-inflammatory activity (IL-8 release and mRNA expression) and morphology (histopathology). 8-Methoxypsoralen (P) and promethazin (P), but not sodium lauryl sulfate (NP) produced cytotoxicity concentration-response curves significantly different between irradiated and nonirradiated tissues. Only irradiated tissues showed morphological damage. Application of tetracyclin (P) in the culture medium, but not topically, induced similar signs of phototoxicity. 6-Methylcoumarine (weak P) was not cytotoxic, yet it increased IL-8 release and mRNA expression only following UVA irradiation. PUVA therapy creams containing 1% 8-Methoxy-psoralen (P) or coal tar (P) decreased viability and induced histologic damage in UVA-exposed tissues. In conclusion, the phototoxic potential of the tested agents was correctly predicted by using a tiered strategy that involves determining cytotoxicity, production of IL-8, and morphological damage following exposure of the HRE to the compounds and UVA light.
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PMID:Assessment of the phototoxic potential of compounds and finished topical products using a human reconstructed epidermis. 1184 89

Although neutrophils are a critical component of the inflammatory process, their functional regulation is incompletely understood. Of note, although pCO2 varies physiologically and pathologically in the neutrophilic milieu, its affect on neutrophil biological processes is unresolved. We demonstrate here that neutrophils respond to hypo- and hypercarbia, (0.04% and 10%) by increasing and decreasing, respectively, intracellular oxidant production (basally and in response to opsonized Escherichia coli and phorbol esters). Further, hypo- and hypercarbia increase and decrease, respectively, the release of IL-8 from LPS-stimulated cells; both effects are attenuated by the carbonic anhydrase inhibitor, acetazolamide. Anion exchange did not restore pH(i) under hypocarbic conditions, however partial restoration of pH(i) under hypercarbic conditions was achieved by Na+/H+ exchange and vacuolar ATPases. Abrogation of pCO2-induced changes in pH(i) prevented hypocarbia-induced generation of reactive oxidant species. These observations suggest that CO2 modifies neutrophil activity significantly by altering pH(i).
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PMID:Ambient pCO2 modulates intracellular pH, intracellular oxidant generation, and interleukin-8 secretion in human neutrophils. 1192 46

Feline peripheral blood mononuclear cells (PBMC)-derived chemotactic factor induced by egg white derivatives (EWD) treatment was analyzed at the protein and messenger ribonucleic acid (mRNA) level. EWD itself was not active chemotactic for feline peripheral blood polymorphonuclear cells (PMN). But chemotaxis of PMN was enhanced by either culture supernatant from PBMC treated with EWD or human recombinant (hr) interleukin (IL)-8. Both hr IL-8 and the culture supernatant from PBMC treated with EWD yielded a distinct band, molecular weight of 6-8kDa, in sodium-dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with 15% loading gel. Therefore, to identify this chemotactic factor, culture supernatant from PBMC treated with EWD was partially purified by anion exchange chromatography on diethylaminoethyl (DEAE)-Sepharose CL-6B and concentrated by ultrafiltration. Only the fraction, which was eluted with 0.3M NaCl, showed a high concentration of total protein and also enhanced the chemotactic activity of PMN. This activity was thereafter designated as eluate. The chemotactic activity of eluate was inhibited by anti-hr IL-8 polyclonal antibody (pAb). A single protein band with 6-8kDa was shown in both the eluate and hr IL-8 when analyzed by SDS-PAGE and Western blotting using anti-hr IL-8 pAb, suggesting that the chemotactic factor for feline PMN is IL-8, 6-8kDa, produced by PBMC treated with EWD. The physicochemical characteristics of eluate were stable in heated (60-100 degrees C), acid (pH 3.0), and alkaline (pH 9.0) conditions. The eluate under these conditions also showed a distinct band in molecular weight of 6-8kDa in SDS-PAGE and Western blotting and was very active in chemotactic activity of PMN.IL-8 mRNA gene expression on feline PBMC was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) assay using a series of oligonucleotides, each 22 mer, derived from feline IL-8. Feline IL-8 mRNA showed low level in 3-h incubation without EWD, but it was increased in a dose-dependent manner by addition of EWD. Following EWD (10 microg/ml) treatment, IL-8 mRNA expression was rapidly increased up to 6h and decreased by 12h although it was not expressed in freshly prepared PBMC. This study strongly suggested that immunoenhancing effect of EWD on chemotactic response of PMN is mediated by feline IL-8, 6-8kDa, produced by PBMC stimulated with EWD. In addition, the expression of feline IL-8 mRNA on PBMC is increased when stimulated with EWD.
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PMID:Feline interleukin-8 expression in peripheral blood mononuclear cells induced by egg white derivatives. 1194 29

The aim of this study was to develop new biocompatible coatings for bone implants by the alternating deposition of oppositely charged polyelectrolytes. Polyelectrolyte films were built up with different terminating layers on which SaOS-2 osteoblast-like cells and human periodontal ligament (PDL) cells were grown. The terminating layer was made of one of the following polyelectrolytes: poly(ethylene imine) (PEI), poly(sodium 4-styrenesulfonate) (PSS), poly(allylamine hydrochloride) (PAH), poly(L-glutamic acid) (PGA), or poly(L-lysine) (PLL). Cell adherence, viability, stability of osteoblast phenotype, and inflammatory response were studied. Adherence and viability were good on all terminating layers except the PEI-terminating layer, which was cytotoxic. Maintenance of osteoblast phenotype marker expression was observed on PSS- and PGA-terminating films for both cell types, whereas downregulation, associated with the induction of Interleukin-8 (IL-8) secretion, was detected on PEI and PAH for both cell types and on PLL for PDL cells. These results suggested a good biocompatibility of PSS- and PGA-ending films for PDL cells and of PSS-, PGA-, and PLL-terminating films for SaOS-2 cells. As a result, polyelectrolyte multilayer films could emerge as new alternatives for implant coatings.
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PMID:Viability, adhesion, and bone phenotype of osteoblast-like cells on polyelectrolyte multilayer films. 1194 25

We previously reported that the fungal particle 1,3-beta-D-glucan derived from Candida albicans, a pathogenic fungus, was obtained by oxidation of the cell wall with sodium hypochlorite (NaClO). It could be solubilized by treatment with dimethylsulfoxide (DMSO). In the present study, we prepared Candida 1,3-beta-D-glucan having different physical properties, and examined the relationship between leukocyte activation and the physicochemical properties. Beta-glucan activated leukocytes significantly more effectively in a particulate than solubilized form in terms of TNF-alpha production by RAW 264.7 cells, hydrogen peroxide production by murine PEC and IL-8 production by human PBMC. Furthermore, we compared the biological activity of the glucan particles oxidized under various conditions. Interestingly, inactive and antagonistic particles were obtained under strong oxidation conditions. However, the inactive particles showed significant agonistic activity on dissolution in DMSO and following lyophilization. These facts strongly suggested that the solubility and assembly of the components influence the immunopharmacological activities of 1,3-beta-D-glucans.
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PMID:Relationship between the physical properties of Candida albicans cell well beta-glucan and activation of leukocytes in vitro. 1234 48

We have previously demonstrated that the pollutant sodium sulfite (Na(2)SO(3)) possesses some proinflammatory properties. This study was conducted in order to elucidate how this environmentally significant chemical can alter human neutrophil cell physiology. Using sensitive ELISAs, we found that Na(2)SO(3) induces the total (intra- and extracellular fractions) production of interleukin-12 (IL-12) and IL-8 but not TNF-alpha, IL-1alpha, or IL-4. IL-8 levels were significantly increased in both fractions while the levels of IL-12 were significantly increased only in the extracellular milieu. In contrast, IL-1Ra levels were significantly decreased in both fractions when cells were treated at the highest Na(2)SO(3) concentration (10 mM). Despite the fact that Na(2)SO(3) was found to increase IL-8 production, it does not induce neutrophil chemotaxis in vitro. Cell surface expression of CD18, CD11a, CD11b, CD11c, CD50, and CD54 was not affected by Na(2)SO(3) treatment. We conclude that Na(2)SO(3) is a modulator of cytokine production but that it does not alter either chemotaxis or cell surface expression of the tested molecules. Our results attest to the importance of systematically monitoring cytokine production from both intracellular and extracellular fractions in pollutant-induced neutrophils, since this could lead to different interpretations.
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PMID:Activation of human neutrophils by the pollutant sodium sulfite: effect on cytokine production, chemotaxis, and cell surface expression of cell adhesion molecules. 1248 90

Proinflammatory cytokines, including interleukin-1 (IL-1) have been implicated in the inflammation that follows corneal alkali injury. The purpose of this series of experiments was to test whether topically applied interleukin-1 receptor antagonist (IL-1ra) could suppress corneal inflammation and promote transparency after alkali injury. Alkali injury was induced on day 0 by application of 1N NaOH to both eyes of Wistar rats (n = 28). Immediately thereafter, eyes received either topical IL-1ra (20 mg ml(-1)) in 0.2% sodium hyaluronate or vehicle alone three times daily during days 0-14. Biomicroscopic features including corneal opacity and neovascularization were assessed using a standard grading scheme. Inflammation was quantified histologically. Corneas excised at day 3 and 7 (randomly selected six eyes in each group per time point studied) were homogenized, and levels of IL-1alpha, IL-1beta, IL-6, IL-8, IL-10, and RANTES were quantified by enzyme-linked immunosorbent assay. Epithelial wound healing was examined by computed analysis of fluorescein stained corneal photographs taken daily until day 14. According to these evaluations, eyes treated with IL-1ra maintained corneal transparency with minimal neovascular invasion. Additionally, corneal damage and cell infiltration were reduced on day 7 (infiltration cells were almost 40% decreased). All cytokine/chemokine levels in IL-1ra treated eyes were significantly lower at day 3, and IL-6 and IL-10 remained significantly lower at day 7 compared to vehicle-treated eyes. IL-1ra treatment retarded epithelial wound healing in the early stage (day 1-4); however, subsequently IL-1ra treated eyes had enhanced healing with full epithelial closure at nearly the same time point as vehicle-treated eyes (day 10). We conclude that local antagonism of IL-1 after alkali injury can significantly decrease corneal inflammation and lead to enhanced corneal transparency.
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PMID:Local suppression of IL-1 by receptor antagonist in the rat model of corneal alkali injury. 1256 3

Occupational exposure to polyvinyl chloride (PVC) dust has been linked to pulmonary disease. The aim of the present study was to investigate, in vitro, the role of additives in the cytotoxicity and the release of inflammatory mediators caused by PVC particles in different cells. We compared two types of emulsion PVC particles (E3 and E8) with their washed (hence, "additive-free") counterparts (W3 and W8). A positive control (crystalline SiO2, Min-U-Sil) and the pure additives, sodium lauryl sulfate (A3) and sodium alkylbenzenesulfonate (A8), were tested concurrently. Cytotoxicity (MTT assay) was assessed in primary cultures of rat alveolar macrophages, rat type II pneumocytes, and human alveolar macrophages (h-AM), and cultures of the A549 cell line (type II cell-derived) and the differentiated THP-1 cell line (macrophage-like). Hemolytic potential was assessed after a 2-h incubation with human erythrocytes. Cytokine release (IL-8, IL-6, and TNF-alpha) by A549 cells, THP-1 cells, and h-AM, was measured by ELISA after 4, 16, 24 and/or 48 h of exposure. Cytotoxicity and hemolytic activity of the washed particles were abolished or markedly decreased compared with their nonwashed forms. In A549 cells, E3 and E8 (2.5 mg/ml) caused a 3-fold increase in IL-8 release and a more than 10-fold increase in IL-6 release, whereas W3 and W8 did not elicit any significant response at similar concentrations. Compared with Min-U-Sil (0.1, 0.5, and 2.5 mg/ml), the response to E3 and E8 occurred later and was slightly lower (IL-8) or much more pronounced (IL-6). A3 and A8 exhibited similar responses to E3 and E8, at concentrations corresponding to those present in the particles. In conclusion, the in vitro cytotoxicity and inflammatory potential of some PVC particles appear to be mostly due to their residual additives.
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PMID:Role of residual additives in the cytotoxicity and cytokine release caused by polyvinyl chloride particles in pulmonary cell cultures. 1260 38

Differentially expressed nucleolar TGF-beta1 target (DENTT) is a recently identified gene whose mRNA is differentially affected by TGF-beta1 in TGF-beta1-responsive human lung cancer cells and who is a new member of the TSPY/TSPY-like/SET/NAP-1 (TTSN) protein superfamily. Here, we report that mouse DENTT mRNA contains a 2031-bp open reading frame that encodes a predicted polypeptide of 677-amino acids with a relative molecular mass of 77,671 Da. The mouse and human DENTT sequences show 77% and 78% homology at the nucleotide and amino acid level, respectively. Mouse DENTT is predicted to be a nuclear protein with two nuclear localization signals (NLS), two coiled-coil regions, and a domain that shows significant identity to a region that defines the TTSN superfamily. Green fluorescent protein (GFP)-tagged full-length mouse DENTT transfected into COS-7 cells showed localization predominantly in the nucleolus. Reverse transcription-polymerase chain reaction amplification, Northern hybridization, and Western blot analyses showed expression of mouse DENTT mRNA and protein throughout mouse embryogenesis. Immunohistochemical staining analysis showed that DENTT is expressed in multiple tissues in a defined spatiotemporal pattern during mouse embryogenesis. The heart and primitive brain were the first organs of the embryo that showed immunoreactivity for the DENTT antibody by day 8 of development (E8). In the developing mouse brain, the choroid plexus was intensely stained for DENTT in all stages of development. The spinal cord and dorsal root ganglia were also positive for DENTT staining beginning in the 11-day-old embryo (E11), where homogeneous immunostaining was observed throughout the developing neurons. By day 16 of development (E16), only a small subset of the neuronal population in the spinal cord and dorsal root ganglia was positively stained for DENTT. DENTT immunoreactivity increased steadily with maturation as the differentiation of cartilage and osteoblasts proceeded and reached a maximum in the growth plate during endochondral ossification. DENTT expression was also detected in multiple rodent cell types in vitro, including mouse F9 embryonal carcinoma (EC) cells. Addition of retinoic acid or sodium butyrate to F9 EC cells showed a rapid decrease in expression of DENTT protein occurring by 1 hr that continued to decrease to almost undetectable levels after 24 hr. Cotransfection of full-length mouse DENTT expression plasmid with 3TPLux or COL7A1Luc Luciferase reporter plasmids into F9 EC cells significantly increased the level of 3TPLux reporter transcription while decreasing the level of COL7A1Luc reporter transcription, suggesting that DENTT may play multiple roles in modulating transcriptional responses. These findings suggest new roles for the TTSN superfamily during embryogenesis and differentiation.
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PMID:Differentially expressed nucleolar TGF-beta1 target (DENTT) in mouse development. 1261 35

In the present study, reconstructed human epidermis (RHE) was used as an in vitro model to discriminate 1-chloro-2,4-dinitrobenzene (DNCB), nickel sulfate (NiSO(4)), oxazolone (OXA), 2,4-dinitrofluorobenzene (DNFB) and 2,4,6-trinitrobenzenesulfonic acid (TNBS) as skin sensitizers from benzalkonium chloride (BC), benzoic acid (BA) and sodium lauryl sulfate (SLS) as skin irritants. Our criteria were (a) the differential IL-1alpha and IL-8 synthesis and release (b) cytotoxicity assessment by MTT assay. When the RHE are topically treated with the sensitizers, very low levels of extra- and intracellular IL-1alpha are observed although they induce significant cytotoxicity. In contrast, they exhibit a sharp maximum of IL-8 release. In the presence of the tested irritants, we observe the inverse cytokine release profile, although they induce dose-dependent cytotoxicity profiles similar to those observed with the sensitizers. Finally, IL-1alpha mRNA upregulation is observed after topical application of both sensitizers and irritants, but only the latter significantly increase extracellular IL-1alpha. In conclusion, our results suggest that the associated determination of IL-8, with IL-1alpha, and MTT conversion are at least necessary to discriminate and classify, in a single assay, irritant and sensitizing agents and represent a potential in vitro alternative to two classical in vivo assays.
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PMID:Analysis of interleukin-1alpha (IL-1alpha) and interleukin-8 (IL-8) expression and release in in vitro reconstructed human epidermis for the prediction of in vivo skin irritation and/or sensitization. 1278 Dec 10


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