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)

Healing of cutaneous wounds requires a complex integrated network of repair mechanisms, including the action of newly recruited leukocytes. Using a skin repair model in adult humans, we investigated the role chemokines play in sequential infiltration of leukocyte subsets during wound healing. At day 1 after injury, the C-X-C chemokines IL-8 and growth-related oncogene alpha are maximally expressed in the superficial wound bed and are spatially and temporally associated with neutrophil infiltration. IL-8 and growth-related oncogene alpha profiles also correlate with keratinocyte migration and subsequently subside after wound closure at day 4. Macrophage infiltration reaches the highest levels at day 2 and is paralleled by monocyte chemoattractant protein-1 mRNA expression in both the basal layer of the proliferative epidermis at the wound margins and mononuclear cells in the wound area. Other monocyte-attracting chemokines such as monocyte chemoattractant protein-3, macrophage inflammatory protein-1alpha and -1beta, RANTES, and 1309 are undetectable. At day 4, perivascular focal lymphocyte accumulation correlates with strong focal expression of the C-X-C chemokines Mig and IP-10. Our results suggest that a dynamic set of chemokines contributes to the spatially and temporally different infiltration of leukocyte subsets and thus integrates the inflammatory and reparative processes during wound repair.
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PMID:Chemokines IL-8, GROalpha, MCP-1, IP-10, and Mig are sequentially and differentially expressed during phase-specific infiltration of leukocyte subsets in human wound healing. 984 75

Alcoholic liver disease is associated with three histologically distinct processes: steatosis (parenchymal fat accumulation), alcoholic hepatitis (characterized by parenchymal infiltration by neutrophil polymorphs), and alcoholic cirrhosis (in which chronic inflammation and fibrosis dominate). Chemokines are cytokines that promote subset-specific leukoycte recruitment to tissues and could therefore play a crucial role in determining which leukocyte subsets are recruited to the liver in alcoholic liver disease. This paper reports that chemokine expression is increased in the liver of patients with alcoholic liver disease and, moreover, that distinct patterns of chemokine expression are associated with the different inflammatory responses to alcohol. Interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1 alpha (MIP-1 alpha), and MIP-1 beta were all detected in the parenchyma at sites of inflammation in alcoholic hepatitis, whereas in alcoholic cirrhosis, chemokines were restricted to inflammatory cells and endothelium in the fibrous septa and portal tracts. In alcoholic hepatitis, chemokine transcription was localized to sinusoidal cells, leukocytes, and fibroblasts in areas of parenchymal inflammation, but hepatocytes, despite staining strongly for chemokine protein, were negative. In alcoholic cirrhosis, chemokine mRNA was detected in portal tract endothelium, leukocytes, and fibroblasts. Thus, alcoholic hepatitis and alcoholic cirrhosis are associated with distinct patterns of chemokine expression that are likely to be important factors in determining whether a patient develops acute parenchymal inflammation and alcoholic hepatitis, or chronic septal inflammation and alcoholic cirrhosis.
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PMID:Distinct patterns of chemokine expression are associated with leukocyte recruitment in alcoholic hepatitis and alcoholic cirrhosis. 987 44

To determine in vivo effects of interleukin (IL)-12 on host inflammatory mediator systems, 4 healthy chimpanzees received recombinant human IL-12 (1 microg/kg) by intravenous injection. IL-12 induced increases in plasma concentrations of IL-15, IL-18, and interferon-gamma (IFN-gamma), plus a marked antiinflammatory cytokine response (IL-10, soluble tumor necrosis factor [TNF] receptors, IL-1 receptor antagonist) and secretion of alpha-chemokines (IL-8, IFN-gamma-inducible protein 10) and beta-chemokines (monocyte chemoattractant protein-1, macrophage inflammatory protein-1beta). In addition, IL-12 elicited neutrophilic leukocytosis, neutrophil degranulation (elastase-alpha1-antitrypsin complexes), coagulation activation (F1 + 2 prothrombin fragment, thrombin-antithrombin III complexes), and fibrinolytic activation (tissue-type plasminogen activator, plasmin-alpha2-antiplasmin complexes). IL-12-induced activation of multiple host mediator systems was found only after 8-24 h, remained detectable until the end of the 48-h observation period, and occurred in the absence of detectable TNF and IL-1beta. These data may contribute to understanding the role of IL-12 in the pathogenesis of sepsis syndrome and the toxicity found after repeated injections of IL-12.
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PMID:Interleukin-12 induces sustained activation of multiple host inflammatory mediator systems in chimpanzees. 995 71

To investigate eosinophil stimulation by chemokines we developed a sensitive assay of leukocyte shape change, the gated autofluorescence/forward scatter assay. Leukocyte shape change responses are mediated through rearrangements of the cellular cytoskeleton in a dynamic process typically resulting in a polarized cell and are essential to the processes of leukocyte migration from the microcirculation into sites of inflammation. We examined the actions of the chemokines eotaxin, eotaxin-2, monocyte chemoattractant protein-1 (MCP-1), MCP-3, MCP-4, RANTES, macrophage inflammatory protein-1alpha (MIP-1alpha), and IL-8 on leukocytes in mixed cell suspensions and focused on the responses of eosinophils to C-C chemokines. Those chemokines acting on CCR3 induced a rapid shape change in eosinophils from all donors; of these, eotaxin and eotaxin-2 were the most potent. Responses to MCP-4 were qualitatively different, showing marked reversal of shape change responses with agonist concentration and duration of treatment. In contrast, MIP-1alpha induced a potent response in eosinophils from a small and previously undescribed subgroup of donors via a non-CCR3 pathway likely to be CCR1 mediated. Incubation of leukocytes at 37 degrees C for 90 min in the absence of extracellular calcium up-regulated responses to MCP-4 and MIP-1alpha in the majority of donors, and there was a small increase in responses to eotaxin. MIP-1alpha responsiveness in vivo may therefore be a function of both CCR1 expression levels and the regulated efficiency of coupling to intracellular signaling pathways. The observed up-regulation of MIP-1alpha signaling via non-CCR3 pathways may play a role in eosinophil recruitment in inflammatory states such as occurs in the asthmatic lung.
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PMID:Differential regulation of eosinophil chemokine signaling via CCR3 and non-CCR3 pathways. 1007 45

Phagocyte recognition, uptake, and nonphlogistic degradation of neutrophils and other leukocytes undergoing apoptosis promote the resolution of inflammation. This study assessed the effects of anti-inflammatory glucocorticoids on this leukocyte clearance mechanism. Pretreatment of "semimature" 5-day human monocyte-derived macrophages (M phi) for 24 h with methylprednisolone, dexamethasone, and hydrocortisone, but not the nonglucocorticoid steroids aldosterone, estradiol, and progesterone, potentiated phagocytosis of apoptotic neutrophils. These effects were specific in that the potentiated phagocytosis of apoptotic neutrophils was completely blocked by the glucocorticoid receptor antagonist RU38486, and glucocorticoids did not promote 5-day M phi ingestion of opsonized erythrocytes. Similar glucocorticoid-mediated potentiation was observed with 5-day M phi uptake of alternative apoptotic "targets" (eosinophils and Jurkat T cells) and in uptake of apoptotic neutrophils by alternative phagocytes (human glomerular mesangial cells and murine M phi elicited into the peritoneum or derived from bone marrow). Importantly, methylprednisolone-mediated enhancement of the uptake of apoptotic neutrophils did not trigger the release of the chemokines IL-8 and monocyte chemoattractant protein-1. Furthermore, longer-term potentiation by methylprednisolone was observed in maturing human monocyte-derived M phi, with greater increases in 5-day M phi uptake of apoptotic cells being observed the earlier glucocorticoids were added during monocyte maturation into M phi. We conclude that potentiation of nonphlogistic clearance of apoptotic leukocytes by phagocytes is a hitherto unrecognized property of glucocorticoids that has potential implications for therapies aimed at promoting the resolution of inflammatory diseases.
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PMID:Glucocorticoids promote nonphlogistic phagocytosis of apoptotic leukocytes. 1009 25

We determined whether human lung fibroblasts might release chemotactic activity for neutrophils (NCA) and monocytes (MCA) in response to bleomycin. The human lung fibroblasts supernatant fluids were evaluated for chemotactic activity by a blind well chamber technique. Human lung fibroblasts released NCA and MCA in a dose- and time-dependent manner in response to bleomycin. Checkerboard analysis of supernatant fluids revealed that both NCA and MCA were chemotactic. Partial characterization revealed that NCA was partly heat labile, trypsin sensitive, and predominantly ethyl acetate extractable. In contrast, MCA was partly trypsin sensitive and ethyl acetate extractable. The release of chemotactic activity was inhibited by lipoxygenase inhibitors and cycloheximide. Molecular sieve column chromatography revealed that both NCA and MCA had multiple chemotactic peaks. NCA was inhibited by leukotriene B4 receptor antagonist and anti-IL-8 and G-CSF Abs. MCA was attenuated by leukotriene B4 receptor antagonist, and monocyte chemoattractant protein-1, GM-CSF, and TGF-beta Abs. Leukotriene B4 receptor antagonist and these Abs inhibited the corresponding m.w. chemotactic activity separated by column chromatography. The concentrations of IL-8, G-CSF, monocyte chemoattractant protein-1, GM-CSF, and TGF-beta in the supernatant fluids significantly increased in response to bleomycin. These data suggest that lung fibroblasts may modulate inflammatory cell recruitment into the lung by releasing NCA and MCA in response to bleomycin.
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PMID:Bleomycin stimulates lung fibroblasts to release neutrophil and monocyte chemotactic activity. 1022 65

IgG deposition at tissue sites characteristically leads to macrophage accumulation and organ injury. Although the mechanism by which deposited IgG induces tissue injury is not known, we have recently demonstrated that deposited IgG stimulates the release of IL-8 and monocyte chemoattractant protein-1 from normal human monocytes, which may drive inflammation. Since IgG also induces macrophage accumulation in these diseases, we hypothesized that deposited IgG protects monocytes from apoptosis. As an in vitro model of the effect of deposited IgG on monocyte survival, monocyte apoptosis was studied after FcgammaR cross-linking. Monocytes cultured on immobilized IgG, which induces FcgammaR cross-linking, were protected from apoptosis, whereas monocytes cultured with equivalent concentrations of F(ab')2 IgG or 50 times higher concentrations of soluble IgG, neither of which induces FcgammaR cross-linking, were not protected. Moreover, this protection was transferable, as supernatants from immobilized IgG-stimulated monocytes protected freshly isolated monocytes from apoptosis and contained functional M-CSF, a known monocyte survival factor. M-CSF mediated the monocyte survival induced by FcgammaR cross-linking, as neutralizing anti-human M-CSF Abs blocked the monocyte protection provided by either immobilized IgG or IgG-stimulated monocyte supernatants. These findings demonstrate a novel mechanism by which deposited IgG targets tissue macrophage accumulation through FcgammaR-mediated M-CSF release. This pathway may play an important role in promoting and potentiating IgG-mediated tissue injury.
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PMID:Regulation of monocyte survival in vitro by deposited IgG: role of macrophage colony-stimulating factor. 1022 67

Kawasaki disease (KD) is a systemic vasculitis preferentially affecting coronary arteries. Extensive monocytes/macrophages infiltrate in the vascular lesions, implying the involvement of a chemotactic cytokine in their recruitment. We investigated the role of monocyte chemoattractant protein-1 (MCP-1, also termed monocyte chemotactic and activating factor) in KD. In the immunohistochemical studies using the cardiac tissues of patients with fatal KD, MCP-1 but not interleukin (IL) -8 or macrophage inflammatory protein-1alpha was localized at the extracellular matrix associated with mononuclear cellular infiltration. The sites of MCP-1 expression correlated with the distribution of the acute inflammation, including early coronary vasculitis. In prospectively studied patients with KD, circulating levels of MCP-1, IL-8, tumor necrosis factor alpha (TNF-alpha), and IL-1alpha were elevated in 73, 77, 57, and 0% of samples before gamma globulin (GG) treatment (400 mg/kg x 5 days = total 2 g/kg), respectively, compared with respective control values. GG treatment correlated with a rapid decrease in the circulating levels of MCP-1 (P = 0.001) but not IL-8 (P = 0.19) or TNF-alpha (P = 0.33). In the sensitive Western blotting, MCP-1 bound to GG. Furthermore, GG inhibited the MCP-1-induced Ca2+ influx in a human monocytic cell line in vitro. These findings suggest a role of MCP-1 in KD, and indicate that GG treatment may block MCP-1 activity, thus alleviating KD vasculitis.
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PMID:Dramatic decrease of circulating levels of monocyte chemoattractant protein-1 in Kawasaki disease after gamma globulin treatment. 1033 83

Human intestinal epithelial cells up-regulate the expression of an inflammatory gene program in response to infection with a spectrum of different strains of enteroinvasive bacteria. The conserved nature of this program suggested that diverse signals, which are activated by enteroinvasive bacteria, can be integrated into a common signaling pathway that activates a set of proinflammatory genes in infected host cells. Human intestinal epithelial cell lines, HT-29, Caco-2, and T84, were infected with invasive bacteria that use different strategies to induce their uptake and have different intracellular localizations (i.e., Salmonella dublin, enteroinvasive Escherichia coli, or Yersinia enterocolitica). Infection with each of these bacteria resulted in the activation of TNF receptor associated factors, two recently described serine kinases, I kappa B kinase (IKK) alpha and IKK beta, and increased NF-kappa B DNA binding activity. This was paralleled by partial degradation of I kappa B alpha and I kappa B epsilon in bacteria-infected Caco-2 cells. Mutant proteins that act as superrepressors of IKK beta and I kappa B alpha inhibited the up-regulated transcription and expression of downstream targets genes of NF-kappa B that are key components of the epithelial inflammatory gene program (i.e., IL-8, growth-related oncogene-alpha, monocyte chemoattractant protein-1, TNF-alpha, cyclooxygenase-2, nitric oxide synthase-2, ICAM-1) activated by those enteroinvasive bacteria. These studies position NF-kappa B as a central regulator of the epithelial cell innate immune response to infection with enteroinvasive bacteria.
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PMID:NF-kappa B is a central regulator of the intestinal epithelial cell innate immune response induced by infection with enteroinvasive bacteria. 1041 47

Newborn animals are resistant to oxygen toxicity. To investigate this phenomenon, the proinflammatory cytokines interleukin (IL)-1 beta, IL-8, and monocyte chemoattractant protein-1 (MCP-1) were measured during newborn rabbit hyperoxic lung injury. Pups were exposed to > 95% O2 for 8-9 days, followed by 60% O2 until 36 days of age. Lung lavage fluid, RNA, and tissue sections were collected at 0, 2, 4, 6, 8, 10, 12, 14, 22, and 36 days. Acute inflammation occurred by 6-10 days of hyperoxia, and fibrosis by 22 days. Northern hybridization of lung homogenates from hyperoxia-exposed pups showed elevated MCP-1 and IL-8 mRNA expression at 6 and 10 days, respectively, compared to age-matched, air-exposed controls. Lavage fluid IL-8 protein also peaked at 10 days, and was strongly correlated to neutrophil numbers in lavage. In situ hybridization revealed elevated IL-1 beta mRNA in macrophages, alveolar epithelial and interstitial cells at 2-10 days, elevated MCP-1 mRNA in similar cell types at 4-8 days, and elevated IL-8 mRNA in these cells and neutrophils at 4-10 days. IL-1 beta and IL-8 expression peaked during peak inflammation, whereas peak MCP-1 expression preceded macrophage influx. Comparing newborn and adult animals' chemokine response may help explain their differences in hyperoxia susceptibility.
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PMID:Discordant pulmonary proinflammatory cytokine expression during acute hyperoxia in the newborn rabbit. 1048 26


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