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)

Ozone exposure can cause inflammation and impaired lung function. Human surfactant protein A (SP-A) may play a role in inflammation by modulating cytokine production by macrophages. SP-A is encoded by two genes, SP-A1 and SP-A2, and several allelic variants have been characterized for each gene. These allelic variants differ among themselves in amino acids that may exhibit differential sensitivity to ozone-induced oxidation and this may produce functional differences. We studied the effects of SP-A variants before and after ozone exposure on the production of tumor necrosis factor (TNF)-alpha and interleukin (IL)-8. These are important proinflammatory cytokines and are expressed by the macrophage-like THP-1 cells. Eight variants were expressed in vitro, characterized by gel electrophoresis, and studied. These included six single-gene SP-A alleles and two SP-A variants derived from both genes. Variants were exposed to ozone at 1 ppm for 4 hr at 37 degrees C, and we compared their ability to stimulate cytokine (TNF-alpha and IL-8) production by THP-1 cells to air-exposed and unexposed SP-A variants. We found that a) SP-A2 variants (1A, 1A(0), 1A(1) stimulate significantly more TNF-alpha and IL-8 production than SP-A1 variants (6A, 6A(2), 6A(4); b) coexpressed SP-A variants (1A(0)/6A(2), 1A(1)/6A(4) have significantly higher activity than single gene products; c) after ozone exposure, all SP-A variants showed a decreased ability to stimulate TNF-alpha and IL-8 production, and the level of the decrease varied among SP-A variants (26-48%); and d) human SP-A from patients with alveolar proteinosis exhibited a minimal decrease (18% and 12%, respectively) in its ability to stimulate TNF-alpha and IL-8 after in vitro ozone exposure. We conclude that biochemical and functional differences exist among SP-A variants, that ozone exposure modulates the ability of SP-A variants to stimulate cytokines by THP-1 cells, and that SP-As from bronchoalveolar lavage (BAL) fluid of certain alveolar proteinosis patients may be oxidized in vivo.
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PMID:The effect of ozone exposure on the ability of human surfactant protein a variants to stimulate cytokine production. 1178 Nov 68

Streptococcus suis capsular type 2 is an important aetiologic agent of swine meningitis, and it has been highlighted as a cause of occupational disease leading to meningitis and fulminant sepsis in humans. The objective of the present work was to study the ability of S. suis type 2 to induce the release of tumour necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1), IL-6, IL-8 and monocyte chemotactic protein one (MCP-1) by human monocytic THP-1 cells. The induction of these five cytokines was dose- and incubation time-dependent, and it was significantly enhanced by pre-treatment of cells with interferon gamma. IL-8 levels were markedly higher compared with those obtained with the other cytokines. However, elevated levels of MCP-1 and IL-6 were also observed. Levels of cytokine induced by heat-killed or live bacteria were similar. Pre-treatment of cells with anti-CD14 monoclonal antibodies suggested that this important host receptor is partially implicated in TNF, IL-1, IL-6 and MCP-1 production, while CD14-independent pathways seem to be responsible for IL-8 production after S. suis stimulation. In addition, blocking studies with anti-TNF and anti-IL-1 antibodies revealed that these cytokines are involved in amplification of the S. suis-induced cytokine cascade. When several different S. suis strains of human or porcine origin were compared, a very heterogeneous pattern of cytokine production was observed. Human strains did not exhibit a clear tendency to induce higher cytokine release by human THP-1 monocytes. The synergistic effect of the up-regulation of cytokines during S. suis meningitis may mediate many of the inflammatory reactions, including the sequestration of leucocytes at the site of infection.
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PMID:CD14-dependent and -independent cytokine and chemokine production by human THP-1 monocytes stimulated by Streptococcus suis capsular type 2. 1187 46

Chemokines such as monocyte chemoattractant protein (MCP) -1 and interleukin (IL)-8 are known to be involved in various processes in atherosclerosis such as plaque formation, plaque rupture, and thrombus formation. We investigated whether a new chemokine, Leukotactin (LKN)-1, is involved in atherosclerosis. We tested the expression of LKN-1 by immunohistochemical methods in carotid atherosclerotic plaque specimen. Induction of pro-inflammatory cytokines, transmigration, and tissue factor (TF) expression were tested in THP-1 cells and human peripheral blood monocytes treated with recombinant human LKN-1. Immunohistochemical analyses revealed that expression of LKN-1 occurs in regions of plaques rich in foam cells. In a Boyden chamber assay, THP-1 cells treated with 0.01--10 nM of LKN-1 transmigrated through gelatin coated filters in a dose dependent manner. LKN-1 also induced the transient expression of TNF-alpha, IL-8, and MCP-1 within 15 min of the treatment of the THP-1 cells. When peripheral blood monocytes were treated with LKN-1, expression levels of TF and TF-mediated procoagulating activity were induced in a time- and dose-dependent manner. These results raise the possibility that LKN-1 is another chemokine that is involved in the atherogenesis. LKN-1 may chemoattract immune cells into the plaque, induce pro-inflammatory cytokines, and produce thrombi by inducing TF expression.
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PMID:A novel chemokine, Leukotactin-1, induces chemotaxis, pro-atherogenic cytokines, and tissue factor expression in atherosclerosis. 1188 7

The family of adrenergic receptors (AR) plays a central role in regulation of the activity of many organ systems. Consequently, regulated expression of the various subtypes of AR is an important mechanism in maintaining homeostasis. Previously, we have shown that alpha(1)-AR triggering of peripheral blood mononuclear cells from patients with juvenile chronic arthritis results in increased IL-6 production. In contrast, alpha(1)-AR agonists do not alter cytokine production by cells of healthy individuals. The aim of the present study was to investigate whether pro-inflammatory cytokines can regulate the expression of mRNA encoding AR of the alpha(1)-family. We show that human THP-1 monocytic cells express mRNA encoding of two of the three cloned subtypes of alpha(1)-AR: alpha(1b)-AR and alpha(1d)-AR mRNA. The cytokines TNF-alpha and IL-1beta decrease level of mRNA for alpha(1d)-AR in THP-1 monocytic cells. In contrast, alpha(1b)-AR mRNA levels are not affected by these two cytokines. Interestingly, IL-1beta and TNF-alpha induce the expression of alpha(1a)-AR mRNA in THP-1 monocytic cells. In human umbilical vein endothelial cells (HUVEC), IL-1beta and TNF-alpha decrease both alpha(1b)-AR and alpha(1d)-AR mRNA levels in HUVEC. alpha(1a)-AR mRNA is not detectable in HUVEC.IL-6 and IL-8, two other pro-inflammatory cytokines tested in this study, do not change alpha(1)-AR subtype levels in HUVEC or monocytic cells. Our data demonstrate that TNF-alpha and IL-1beta can regulate expression of alpha(1)-AR mRNA and that cytokine regulation of alpha(1)-AR expression is subtype- and tissue-specific.
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PMID:Cytokines regulate alpha(1)-adrenergic receptor mRNA expression in human monocytic cells and endothelial cells. 1196 Jun 42

The inflammatory response associated with Chlamydia trachomatis genital infections is thought to be initiated by the release of proinflammatory cytokines from infected epithelial cells. This study focuses on the interactions between C. trachomatis-infected HeLa cells and immune cells involved in the early stages of infection, i.e., neutrophils and macrophages. First, we showed that the expression of interleukin-11 (IL-11), an anti-inflammatory cytokine mainly active on macrophages, was upregulated at the mRNA level in the genital tracts of infected mice. Second, incubation of differentiated THP-1 (dTHP-1) cells or monocyte-derived macrophages (MdM) with basal culture supernatants from C. trachomatis serovar E- or serovar L2-infected HeLa cells resulted in macrophage activation with a differential release of tumor necrosis factor alpha (TNF-alpha) and upregulation of indoleamine 2,3-deoxygenase (IDO) but not of Toll-like receptor 2 and 4 mRNA expression. Third, coculture of infected HeLa cells with dTHP-1 cells resulted in a reduction in chlamydial growth, which was more dramatic for serovar E than for L2 and which was partially reversed by the addition of anti-TNF-alpha antibodies for serovar E or exogenous tryptophan for both serovars but was not reversed by the addition of superoxide dismutase or anti-IL-8 or anti-IL-1beta antibodies. A gamma interferon-independent IDO mRNA upregulation was also detected in dTHP-1 cells from infected cocultures. Lastly, with a two-stage coculture system, we found that (i) supernatants from neutrophils added to the apical side of infected HeLa cell cultures were chlamydicidal and induced MdM to express antichlamydial activity and (ii) although polymorphonuclear leukocytes released more proinflammatory cytokines in response to serovar E- than in response to L2-infected cells, MdM were strongly activated by serovar L2 infection, indicating that the early inflammatory response generated with a nondisseminating or a disseminating strain is different.
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PMID:Differences in innate immune responses (in vitro) to HeLa cells infected with nondisseminating serovar E and disseminating serovar L2 of Chlamydia trachomatis. 1201 Oct 19

Phagocytosis of apoptotic cells by macrophages leads to the production of anti-inflammatory cytokines, thereby preventing inflammation. In this study, we demonstrate that human serum potentiates the production of anti-inflammatory cytokines, IL-10 and TGF-beta, by PMA-treated THP-1 cells and human monocyte-derived macrophages in response to apoptotic cells, which results in great suppression of the production of proinflammatory cytokine IL-8. Human IgG but not its F(ab)'(2) suppressed the IL-8 production. Pretreatment of macrophages but not apoptotic cells with human serum or human IgG caused the suppression, suggesting that immune complex may not be formed with apoptotic cells. When FcgammaRI was specifically down-modulated by a monoclonal antibody, M22, the potentiating effects of human serum and human IgG on the anti-inflammatory cytokine production and the suppressive effects on IL-8 production were completely abolished. Thus, human IgG and FcgammaRI appear to be critical in leading to the production of anti-inflammatory cytokines by macrophage in response to apoptotic cells.
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PMID:Potentiation by human serum of anti-inflammatory cytokine production by human macrophages in response to apoptotic cells. 1205 Jan 79

Propionibacterium acnes (P. acnes) causes an inflammatory acne that is characterized by massive neutrophilic infiltration. IL-8 is thought to play an important role in the pathophysiology of P. acnes, although the mechanisms by which P. acnes up-regulates the release of IL-8, a neutrophilic chemokine, from target cells is not well understood. In this study, we investigated the mechanisms through which heat-killed P. acnes induces IL-8 production in THP-1 cells (a human monocytic cell line). We found that P. acnes is able to directly induce IL-8 production and IL-8 mRNA expression in human monocytic cells in a dose- and time-dependent manner through a mechanism requiring transcription factor NF-kappaB activation. Additionally, P. acnes-induced IL-8 secretion was inhibited by roxithromycin, a macrolide antibiotic, and its inhibitory effect seemed to be partially associated with the inhibition of P. acnes-induced NF-kappaB activation. This is the first study to show that NF-kappaB activation is involved in the IL-8 production of monocytic cells stimulated by P. acnes.
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PMID:Propionibacterium acnes-induced IL-8 production may be mediated by NF-kappaB activation in human monocytes. 1208 10

Bartonella henselae is responsible for various disease syndromes that loosely correlate with the immune status of the host. In the immunocompromised individual, B. henselae-induced angiogenesis, or bacillary angiomatosis, is characterized by vascular proliferative lesions similar to those in Kaposi's sarcoma. We hypothesize that B. henselae-mediated interaction with immune cells, namely, macrophages, induces potential angiogenic growth factors and cytokines which contribute in a paracrine manner to the proliferation of endothelial cells. Vascular endothelial growth factor (VEGF), a direct inducer of angiogenesis, and interleukin-1beta (IL-1beta), a potentiator of VEGF, were detected within 12 and 6 h, respectively, in supernatants from phorbol 12-myristate 13-acetate-differentiated human THP-1 macrophages exposed to live B. henselae. Pretreatment of macrophages with cytochalasin D, a phagocytosis inhibitor, yielded comparable results, suggesting that bacterium-cell attachment is sufficient for VEGF and IL-1beta induction. IL-8, an angiogenic cytokine with chemotactic properties, was induced in human microvascular endothelial cells (HMEC-1) within 6 h of infection, whereas no IL-8 induction was observed in infected THP-1 cells. In addition, conditioned medium from infected macrophages induced the proliferation of HMEC-1, thus demonstrating angiogenic potential. These data suggest that Bartonella modulation of host or target cell cytokines and growth factors, rather than a direct role of the bacterium as an endothelial cell mitogen, is the predominant mechanism responsible for angiogenesis. B. henselae induction of VEGF, IL-1beta, and IL-8 outlines a broader potential paracrine angiogenic loop whereby macrophages play the predominant role as the effector cell and endothelial cells are the final target cell, resulting in their proliferation.
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PMID:Induction of a potential paracrine angiogenic loop between human THP-1 macrophages and human microvascular endothelial cells during Bartonella henselae infection. 1211 69

Monocytic cells were stimulated with IgG-OVA equivalence immune complexes, mAb reacting with FcgammaRI, FcgammaRIIA, and FcgammaRIII, LPS, TNF-alpha, and the combination of ionomycin and phorbol ester, to address their effects on the expression of the mRNAs encoding for chemokines. Stimulation of monocytes with immune complexes induced a rapid expression of macrophage-inflammatory protein (MIP)-1alpha, MIP-1beta, and IL-8 mRNAs. In contrast, RANTES mRNA was already detectable in resting cells and only increased after 16 h of stimulation. A similar pattern was observed following homotypic stimulation of FcgammaR with mAb reacting with FcgammaRI and FcgammaRIIA, but not with a mAb reacting with FcgammaRIII, a subtype of receptor not expressed in THP-1 cells, thus indicating that both FcgammaRI and FcgammaRIIA are involved in the response. The pattern of chemokine induction elicited by LPS and the combination of ionomycin and PMA showed some similarities to those produced by FcgammaR cross-linking, although expression of IFN-gamma-inducible protein 10 mRNA was also observed in response to those agonists. The production of MIP-1alpha, MIP-1beta, and RANTES proteins encompassing the induction of their mRNAs was confirmed by specific ELISA. Experiments to address the transcription factors involved in the regulation of MIP-1alpha using pharmacological agents and EMSA showed the possible involvement of CCAAT/enhancer-binding protein beta sites and ruled out the functional significance of both NF-AT and AP-1 sites.
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PMID:Activation of monocytic cells through Fc gamma receptors induces the expression of macrophage-inflammatory protein (MIP)-1 alpha, MIP-1 beta, and RANTES. 1221 53

Inhaled diesel exhaust particles (DEP) exert proinflammatory effects in the respiratory tract. This effect is related to the particle content of redox cycling chemicals and is involved in the adjuvant effects of DEP in atopic sensitization. We demonstrate that organic chemicals extracted from DEP induce oxidative stress in normal and transformed bronchial epithelial cells, leading to the expression of heme oxygenase 1, activation of the c-Jun N-terminal kinase cascade, IL-8 production, as well as induction of cytotoxicity. Among these effects, heme oxygenase 1 expression is the most sensitive marker for oxidative stress, while c-Jun N-terminal kinase activation and induction of apoptosis-necrosis require incremental amounts of the organic chemicals and increased levels of oxidative stress. While a macrophage cell line (THP-1) responded in similar fashion, epithelial cells produced more superoxide radicals and were more susceptible to cytotoxic effects than macrophages. Cytotoxicity is the result of mitochondrial damage, which manifests as ultramicroscopic changes in organelle morphology, a decrease in the mitochondrial membrane potential, superoxide production, and ATP depletion. Epithelial cells also differ from macrophages in not being protected by a thiol antioxidant, N-acetylcysteine, which effectively protects macrophages against cytotoxic DEP chemicals. These findings show that epithelial cells exhibit a hierarchical oxidative stress response that differs from that of macrophages by more rapid transition from cytoprotective to cytotoxic responses. Moreover, epithelial cells are not able to convert N-acetylcysteine to cytoprotective glutathione.
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PMID:Comparison of the pro-oxidative and proinflammatory effects of organic diesel exhaust particle chemicals in bronchial epithelial cells and macrophages. 1237 Mar 90


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