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)

In American cutaneous leishmaniasis (ACL), Leishmania parasites enter the epidermis of the host via the bite of infected sandflies. Immune responses against the parasite vary from "effective" in localized (LCL) to a state of "selective anergy" in diffuse (DCL) cutaneous leishmaniasis, whereas the intermediate muco-cutaneous form (MCL) is characterized by an exacerbated cell-mediated immunity. We have shown that in LCL epidermis, Langerhans cells (LC) are increased, HLA-DR is universally expressed and intercellular adhesion molecule-1 (ICAM-1) immunoreactivity is distributed in patches. In addition, mRNA for IL-1 beta, IL-8, TNF alpha, TNF beta, and INF gamma may be detected in epidermal sheets by reverse transcriptase followed by polymerase chain reaction (RT-PCR). In contrast, DCL epidermis shows fewer LC than LCL epidermis, and expression of ICAM-1, HLA-DR, and IL-1 beta mRNA cannot be detected. MCL lesions show a mucosal epithelium lacking LC, but ICAM-1 is universally expressed. The clinical manifestations of ACL can be reproduced experimentally in different strains of inbred mice. In healthy mice, we have shown a positive correlation between LC and dendritic epidermal T cells (DETC) numbers. This correlation was not, however, observed in L. mexicana-infected mice, suggesting that infection alters the balance between the two cell types. In addition, agents that modulate LC and DETC cell densities change the development of experimental leishmaniasis. These results suggest that the epidermis is essential in determining the type of immune response that is developed against the Leishmania parasites.
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PMID:Epidermal compromise in American cutaneous leishmaniasis. 135 84

In this paper we studied the relationship between doses (5-40Gy) and indices of nuclear damage in lymphocyte of human peripheral blood irradiated by 10 Mev of electron beam to explore possibility of establishing biodosimeter of overdose irradiation. The main results are as follows: (1) The frequency of micronucleated cell (MNCF), the frequency of irregular nucleus (INF), the frequency of pyknotic nucleus (PNF), the frequency of karyorrhetic nucleus (KNF) and the frequency of nuclear anomalies (NAF = MNCF + INF + PNF + KNF) increased along with increase of irradiation dose. Within the range of 0-20Gy indices of nuclear damages which were linear with irradiation doses are NAF (P less than 0.01), MNF (P less than 0.01), INF (P less than 0.05) and KNF (r = 0.8972), P greater than 0.05). Within the range of 0-40Gy the index of nuclear damage which was linear with irradiation dose was PNF (P less than 0.01) alone. (2) As compared with chromosome aberration analysis nuclear anomaly test is a more rapid and convenient assay, and can detect overdose radiation damage using chromosome analysis.
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PMID:[Preliminary studies of dose-effect relationship in overdose irradiation of electron beam with high energy--comparative observation of several indices of nuclear damage in lymphocyte of human peripheral blood]. 152 49

The liver participates in inflammation via the elaboration of acute phase proteins from hepatocytes in response to IL-1, TNF-alpha, and IL-6/INF-beta 2/hepatocyte-stimulating factor. In addition, some inflammatory states of the liver are characterized by leukocyte infiltrates. Here we demonstrate that human hepatocyte lines are capable of expressing mRNA and biologic activity for a neutrophil chemotactic factor (NCF)/IL-8 in response to the inflammatory mediators IL-1 alpha, IL-1 beta, and TNF. Two human hepatoma cell lines (SK-Hep and Hep-G2) displayed a time- and dose-dependent increase in steady state levels of NCF/IL-8 mRNA and secretion of chemotactic activity in response to TNF and IL-1. Neutralizing antibody to NCF/IL-8 inhibited hepatocyte-derived chemotactic activity by 88%. In contrast to IL-1 and TNF, hepatocytes did not respond to LPS or IL-6 within the time and dose parameters used above. Although the expression of NCF/IL-8 mRNA (1.8 kb) was first detectable between 1 and 2 h poststimulation, significant chemotactic bioactivity was not observed until about 4 h. Heat-inactivated (100 degrees C, 30 min) cytokine failed to induced NCF/IL-8 mRNA synthesis, and cotreatment of cells with cytokine and cycloheximide super-induced NCF/IL-8 mRNA while inhibiting production of bioactivity. Thus, NCF/IL-8 expression is a primary induction phenomenon. Our data demonstrate the stimulus specific induction of NCF/IL-8 in hepatocytes and suggest that cytokine cell-to-cell communication circuits may be important in neutrophil-mediated inflammatory processes in the liver.
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PMID:Cytokine-induced gene expression of a neutrophil chemotactic factor/IL-8 in human hepatocytes. 215 28

Recently, we have isolated and characterized a set of cDNA clones which encode lipopolysaccharide-inducible proteins in murine peritoneal macrophages. Here, we report the sequence and identification of one of these cDNAs previously termed C7. Nucleotide sequence analysis revealed an open reading frame encoding a predicted polypeptide composed of 98 amino acids, which contained a 21 amino acid residue signal peptide, indicating approximately 9 kDa of mature protein. The deduced protein sequence showed homology (67% identity, 77% considering conservative amino acid changes) with the human INF gamma-inducible gene IP-10, a member of the recently described superfamily of chemotactic and mitogenic proteins which includes platelet factor 4, monocyte-derived neutrophil chemotactic factor (NAF, NAP-1, IL-8), and MGSA/gro/KC. Thus C7 would appear to represent the murine homologue of the human IP-10 gene or a very closely related gene.
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PMID:A macrophage LPS-inducible early gene encodes the murine homologue of IP-10. 218 6

HuGRO, IL-8 and gamma-IP-10 belong to a recently described superfamily of genes encoding a group of cytokines with inflammatory, growth regulating and/or leukocyte chemotactic properties (chemokines). We studied huGRO, IL-8 and gamma-IP-10 gene expression in unstimulated and stimulated (TNF alpha, INF gamma, TNF alpha + IFN gamma, IL-1 beta, PMA and LPS) normal human keratinocytes by Northern blot analysis. The mRNA for none of the three chemokines was detectable in unstimulated keratinocytes, but considerably elevated levels of huGRO and IL-8 mRNA, but not of gamma-IP-10 mRNA, were found in the presence of cycloheximide, indicating that huGRO and IL-8 mRNA, but not gamma-IP-10 mRNA, are constitutively produced. gamma-IP-10 mRNA was exclusively induced by IFN gamma, with a strong and transient rise between 8 and 18 h, and superinduced by the combination of IFN gamma and TNF alpha, indicating marked synergism. Both huGRO and IL-8 mRNA were induced by TNF alpha and PMA (a strong and transient rise between 2 and 8 h), but not by IFN gamma or LPS. The combination of TNF alpha and IFN gamma did not show a synergistic effect. In addition, IL-1 beta transiently upregulated huGRO mRNA but failed to induce IL-8 mRNA. Using specific oligonucleotides for alpha, beta and gamma huGRO, TNF alpha was found to induce all three forms, alpha and beta to an equal extent and gamma to a lesser extent.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Human growth factor (huGRO), interleukin-8 (IL-8) and interferon-gamma-inducible protein (gamma-IP-10) gene expression in cultured normal human keratinocytes. 786 61

1. LPS phase I trial revealed MTD I of 1.0 ng/kg body weight and MTD II of 5.0 ng/kg body weight, the latter given together with ibuprofen (1,600 mg). 2. LPS phase II trial, using 4,0 ng/kg body weight plus ibuprofen in a biweekly schedule didn't show any response in patients with non-small cell lung cancer but 1 CR and 2 PR (13% response rate) in colorectal cancer patients. 3. The LPS tolerance is specific for each cytokine and mediator in regard to the kinetic and degree of its development. INF-gamma prevents the tolerance development to several cytokines with the exception of IL-8. 4. No tolerance was found in cell adhesion, phospholipase A2, and soluble TNF receptor I and II. Priming of ex vivo cytokine production of cytokines was found in mononuclear cells. 5. Synthetic LPS partial structure SDZ-MRL 953 (I) induces a cytokine pattern, which is profoundedly different from that of LPS, (II) with an inverse TNF to G-CSF relation, (III) is (without any ibuprofen treatment) remarkably low toxic, (IV) and downregulates the TNF-response to LPS markedly.
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PMID:Endotoxin (Salmonella abortus equi) in cancer patients. Clinical and immunological findings. 852 30

Cytokines are a heterogenous group of polypeptide mediators that have been associated with activation of numerous functions, including the immune system and inflammatory responses. The cytokine families include, but are not limited to, interleukins (IL-I alpha, IL-I beta, ILIra and IL-2-IL-15), chemokines (IL-8/ NAP-I, NAP-2, MIP-I alpha and beta, MCAF/MCP-1, MGSA and RANTES), tumor necrosis factors (TNF-alpha and TNF-beta), interferons (INF-alpha, beta and gamma), colony stimulating factors (G-CSF, M-CSF, GM-CSF, IL-3 and some of the other ILs), growth factors (EGF, FGF, PDGF, TGF alpha, TGF beta and ECGF), neuropoietins (LIF, CNTF, OM and IL-6), and neurotrophins (BDNF, NGF, NT-3-NT-6 and GDNF). The neurotrophins represent a family of survival and differentiation factors that exert profound effects in the central and peripheral nervous system (PNS). The neurotrophins are currently under investigation as therapeutic agents for the treatment of neurodegenerative disorders and nerve injury either individually or in combination with other trophic factors such as ciliary neurotrophic factor (CNTF) or fibroblast growth factor (FGF). Responsiveness of neurons to a given neurotrophin is governed by the expression of two classes of cell surface receptor. For nerve growth factor (NGF), these are p75NTR (p75) and p140trk (referred to as trk or trkA), which binds both BDNF and neurotrophin (NT)-4/5, and trkC receptor, which binds only NT-3. After binding ligand, the neurotrophin-receptor complex is internalized and retrogradely transported in the axon to the soma. Both receptors undergo ligand-induced dimerization, which activates multiple signal transduction pathways. These include the ras-dependent pathway utilized by trk to mediate neurotrophin effects such as survival and differentiation. Indeed, cellular diversity in the nervous system evolves from the concerted processes of cell proliferation, differentiation, migration, survival, and synapse formation. Neural adhesion and extracellular matrix molecules have been shown to play crucial roles in axonal migration, guidance, and growth cone targeting. Proinflammatory cytokines, released by activated macrophages and monocytes during infection, can act on neural targets that control thermogenesis, behavior, and mood. In addition to induction of fever, cytokines induce other biological functions associated with the acute phase response, including hypophagia and sleep. Cytokine production has been detected within the central nervous system as a result of brain injury, following stab wound to the brain, during viral and bacterial infections (AIDS and meningitis), and in neurodegenerative processes (multiple sclerosis and Alzheimer's disease). Novel cytokine therapies, such as anticytokine antibodies or specific receptor antagonists acting on the cytokine network may provide an optimistic feature for treatment of multiple sclerosis and other diseases in which cytokines have been implicated.
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PMID:Neurotrophins and their receptors in nerve injury and repair. 910 50

The results of the present study, summarized in Table 2, demonstrate that different species and strains of rodents (rats and mice) and birds (chickens) exhibit rather specific fever response. Systemic administration of LPS caused monophasic elevation in Tb of chickens, biphasic changes in Tb of rats (initial drop followed by an increase in Tb), whereas mice failed to develop hyperthermia and responded by a decreased Tb. The LPS-induced alterations in hypothalamic prostanoid synthesis were also rather species-specific and differ markedly even between the two strains of mice. We failed to find a common direct correlation between LPS-induced changes in Tb and hypothalamic prostanoid production in rodents (rats and mice). This observation is supported by our recent study on age-related changes in fever response in rats, where we found that hypothalami of LPS-treated old and young adult rats produced similar amounts of PGE2 and PGI2, in spite of more pronounced and prolonged hypothermia, and a delayed elevation in Tb of old rats, as compared with young (Fraifeld et al., 1995b). Moreover, the hypothalamus of febrile chickens did not display any detectable activation of PGE2 production, suggesting that PGE2 is not a common central mediator of fever in homeotherms (Fraifeld et al., 1995a). Apparently, the actual body temperature not always reflects the functional state of central thermostat, and increased PGE2 production in hypothalamus would not directly, at least in rodents, lead to body temperature elevation. Furthermore, peripheral effects, including PG-mediated ones, of pyrogens can interfere and even overcome their centrally-mediated effects (Morimoto et al., 1991; Burysek et al., 1993). Previously, we have shown that no additional elevation in hypothalamic PGE2 production occurs in response to doses of LPS over 10 micrograms in rats and 25 micrograms in mice, while the increased doses led to further changes in Tb response (Kaplanski et al., 1993). Morimoto et al. (1991) have considered that PGE2 acts centrally to cause fever and peripherally to cause hypothermia, and, hence, these opposing actions, both being induced by LPS, may act together to determine the final thermoregulatory response. Other possibilities could be related to counterbalance of endogenous antipyretics (Kluger, 1991; Kozak et al., 1995), that may occur not only at the level of thermoregulatory center but also outside the CNS (Klir et al., 1995), and to the existence of PG-independent mechanisms of LPS fever. The latter have been shown for IL-8 (Rothwell et al., 1990; Zampronio et al., 1994) and MIP-1 (Davatelis et al., 1989; Minano et al., 1990; Hayashi et al., 1995; Lopez-Valpuesta and Myers, 1995), which are, apparently, mediated via CRF (Strijbos et al., 1992; Zampronio et al., 1994), and INF-alpha, mediated via the opioid receptor mechanisms (Hori et al., 1991, 1992). However, it has been shown recently that in different species the same pyrogenic cytokines (IL-8) may induced fever via different, PG-independent (in rats; Zampronio et al., 1994) or PG-dependent (in rabbits; Zampronio et al., 1995) mechanisms. It should be noted that fever response is not always accompanied by an elevation in Tb. The final effect of pyrogens on body temperature depends upon the balance between heat production and heat loss, which in turn is highly dependent upon body size and ambient temperature, especially in small animals. Perhaps, the hypothermic response observed in our mice and rats at 22 degrees C may be in part attributed to ambient temperature, which was below a thermoneutral zone. The reduced febrile response is considered, at least in part, to contribute to an increased mortality and prolonged recovery from infections (Kluger, 1986). From this point, it is difficult to suggest whether the hypothermia observed in our mice and rats could be of somewhat adaptive significance. It has been shown that at the ambient temperature of 30 degrees C, Swiss Webster mice can re
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PMID:Brain eicosanoids and LPS fever: species and age differences. 963 34

Interactions between infiltrating T cells and keratinocytes via the secretion of the TH1 cytokines interleukin (IL) 2 and interferon gamma (INF-gamma), the keratinocyte growth factor transforming growth factor alpha (TGF-alpha) and the cytokines IL-6 and IL-8 are thought to be the predominant mechanisms inducing skin lesions in psoriatic patients. Systemic treatment of psoriasis with fumaric acid derivatives (FAEs) has been reported to be effective in the treatment of psoriasis, but the mode of action is still unknown. To clarify this phenomenon, keratinocytes from psoriatic patients as well as from healthy volunteers were mono- and cocultured with HUT 78 T cells with/without the addition of FAEs; the cytokine concentrations were then measured in the culture supernatants. Furthermore, mRNA expression was determined in epidermal growth factor (EGF) -activated keratinocytes as well as in phytohaemagglutinin (PHA)-activated HUT 78 T cells. Only dimethylfumarate (DMF) diminished IL-6 and TGF-alpha secretion in the psoriatic cocultures. However, it did not have this effect on cocultures from control subjects or on monocultures. DMF suppresses EGF-induced TGF-alpha mRNA induction in psoriatic keratinocytes. DMF inhibited INF-gamma secretion in all cultures but stimulated the IL-10 secretion. This immunomodulation away from the TH1 cytokine IFN-gamma to the TH2 cytokine IL-10 was confirmed in HUT 78 T cells by Northern blot analysis. An increased number of eosinophils is a known side-effect in patients treated with this drug, suggesting a clinical relevance of this immunomodulation in vivo. This immunomodulation and the suppression of cytokines from the psoriatic cytokine network could be responsible for the beneficial effect of DMF in the treatment of a hyperproliferative and TH1 cytokine-mediated skin disease.
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PMID:The antipsoriatic agent dimethylfumarate immunomodulates T-cell cytokine secretion and inhibits cytokines of the psoriatic cytokine network. 976 81

When macrophages derived from rat bone marrow were cultured in the presence of polyanions such as acetyl lignin (EP3), sulfonyl lignin (LS) or dextran sulfate (DS), the cells secreted TNF-alpha, IL-8 and nitric oxide (NO). EP3 had a dose-dependent effect on the secretion of TNF-alpha, IL-8 and NO. EP3 significantly affected secretion at concentrations greater than 5 microg/ml. The EP3 effect was at its maximum between concentrations of 50 and 100 microg/ml. LS and DS induced a slight increase in the secretion of cytokines and NO at a concentration of 100 microg/ml. The use of the reverse-transcription polymerase chain reaction (RT-PCR) showed that the increases in cytokine and NO secretion were due to an increase in cytokine mRNAs or NO synthase mRNA. Anti-TNF-alpha antibodies partially inhibited NO secretion by EP3-activated macrophages, although IL-8 secretion was independent of antibody treatment. The secretion of TNF-alpha and NO was also unaffected by the addition of anti-IL-8 antibodies. The addition of interferon-gamma (IFN-gamma) to the culture medium did not alter TNF-alpha and NO secretion by the EP3-activated macrophages, however, IL-8 secretion was increased when a low concentration of IFN-gamma (0.2 U/ml) was added, but was reduced in the presence of a high concentration of IFN-gamma (2000 U/ml). IFN-gamma produced similar effects on cytokine and NO secretion in macrophages activated with lipopolysaccharide (LPS). Therefore, it is concluded that macrophages treated with polyanions secrete cytokines and NO, and that INF-gamma is involved in the regulatory mechanism of cytokine and NO secretion.
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PMID:Secretion of TNF-alpha, IL-8 and nitric oxide by macrophages activated with polyanions, and involvement of interferon-gamma in the regulation of cytokine secretion. 1043 3


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