The Regulation of Interleukin-8 by Hypoxia in Human Macrophages—A Potential Role in the Pathogenesis of the Acute Respiratory Distress Syndrome (ARDS)

Hirani, Nik; Antonicelli, Frank; Strieter, Robert M.; Wiesener, Michael S.; Ratcliffe, Peter J.; Haslett, Christopher; Donnelly, Seamas C

doi:10.1007/bf03401959

Cited by 98 publications

(81 citation statements)

References 55 publications

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“…Although monocytes contribute to the development of atherosclerotic lesions, IL-8 is a powerful trigger for firm adhesion of monocytes to vascular endothelium (10). It has been shown that hypoxia induces expression and/or generation of IL-8 (13,30), indicating that OSAS-associated desaturation could lead to upregulatation of IL-8 expression. In addition, one could presume that the effective therapy for OSAS may attenuate hypoxic stress, which may prevent the development of vascular lesions via the reduction of IL-8 production.…”

Section: Discussionmentioning

confidence: 99%

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Effects of obstructive sleep apnea on circulating ICAM-1, IL-8, and MCP-1

Ohga

Tomita

Wada

et al. 2003

Journal of Applied Physiology

305

180

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structive sleep apnea syndrome (OSAS) is one of the most important risk factors of cardiovascular disorders. In the treatment of OSAS, nasal continuous positive airway pressure (nCPAP) has been widely used and found to be effective. In the present study, we hypothesized that the hypoxic stress caused by obstructive sleep apnea would increase circulating intercellular adhesion molecule-1 (ICAM-1), interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1) in untreated OSAS patients compared with an age-matched control group. In addition, we hypothesized that nCPAP may decrease OSAS-induced hypoxic stress and mediators. To examine these hypotheses, we measured circulating ICAM-1 and IL-8 before and after nCPAP therapy in OSAS patients. We observed that nCPAP decreased apnea, desaturation, and the circulating ICAM-1 and IL-8 levels in OSAS patients. The circulating levels of ICAM-1, IL-8, and MCP-1 in untreated OSAS patients were significantly greater than those in the controls. These observations suggest that nCPAP therapy could reduce OSAS-induced hypoxia and generation of inflammatory mediators. Treatment of OSAS using nCPAP can be, therefore, a potential approach to decrease risk of the progression of OSAS-associated disorders. cytokines; cardiovascular disorders; ischemic heart disease; desaturation magnitude; hypoxic stress; intracellular adhesion molecule-1; monocyte chemoattractant protein-1; interleukin-8

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Section: Discussionmentioning

confidence: 99%

“…Hypoxic stress increases the adherence of neutrophils to endothelial cells, and this increased adherence is mediated by proinflammatory mediators, including ICAM-1 (2) and IL-8 (13,30). Furthermore, it has been reported that hypoxia induces the synthesis and expression of both ICAM-1 and IL-8 via the activation of nuclear transcription factor (NF)-B (7,36,37).…”

mentioning

confidence: 99%

Effects of obstructive sleep apnea on circulating ICAM-1, IL-8, and MCP-1

Ohga

Tomita

Wada

et al. 2003

Journal of Applied Physiology

305

180

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“…42 The formation of MCP-1 is reduced by hypoxia in ovarian cancer cells, 43 macrophages 44,45 and human synovial fibroblasts. 46 However, hypoxia upregulated MCP-1 formation in cultured neonatal mouse cardiac myocytes and MCP-1 decreased hypoxia-induced cell death.…”

Section: Discussionmentioning

confidence: 99%

Regulation of monocyte chemoattractant protein 1 (MCP-1) release by explants of human visceral adipose tissue

Fain

Madan

2005

Int J Obes

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BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) is a chemokine involved in monocyte recruitment during inflammation whose plasma level is elevated in obesity. OBJECTIVE: The present studies were designed to examine the release of MCP-1 in primary culture by explants of visceral adipose tissue from morbidly obese women. RESULTS: Most of the MCP-1 released by adipose tissue explants was derived from the nonfat cells in adipose tissue. The release of MCP-1 by adipose tissue explants was upregulated almost five-fold between 3 and 48 h of incubation. Approximately half of this upregulation was due to the release of endogenous tumor necrosis factor a (TNFa) and IL-1b based on the ability of a combination of a soluble TNFa receptor (etanercept) and a blocking antibody against IL-1b to reduce MCP-1 release. The release of MCP-1 over 48 h was unaffected by insulin or dexamethasone but significantly reduced by the combination of both agents. MCP-1 release was reduced by 60% in the presence of an inhibitor of the nuclear factor kB (NF-kB) pathway. There were no significant effects of inhibitors of p44/42 mitogen-activated protein kinase (ERK), Jun N-terminal kinase (JNK) and p38 mitogenactivated protein kinase (p38 MAPK) pathways on MCP-1 release. However, inhibition of MCP-1 release in the presence of inhibitors of both the p38 MAPK and NF-kB pathways was greater than that seen with only the NF-kB inhibitor. DISCUSSION: The present data shows that MCP-1 formation is upregulated over a 48-h incubation of primary explants of visceral adipose tissue. Half of this upregulation is dependent upon endogenous TNFa and Il-1b and involves the p38 MAPK and NF-kB pathways.

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“…CXCL8 protein is upregulated in human MDM within 2 hr of exposure to hypoxia, via a mechanism involving the transcription factors AP-1 and C/EBP but not NFjB or HIF. 80 Furthermore, primary murine macrophages respond to hypoxia by secreting elevated levels of MIP-2 (murine CXCL1) via an NFjB-mediated mechanism. 61 These CXC chemokines have been shown to stimulate endothelial and tumor cell proliferation and migration in vitro, and revascularization in vivo and have been implicated in mediating nonsmall-cell lung tumor-associated angiogenesis.…”

Section: Tam Gene Expression In Response To Tumor Hypoxiamentioning

confidence: 99%

Macrophage migration and gene expression in response to tumor hypoxia

Murdoch

Lewis

2005

Intl Journal of Cancer

183

143

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Monocytes are recruited into tumors from the circulation along defined chemotactic gradients and they then differentiate into tumor-associated macrophages (TAMs). Recent evidence has shown that large numbers of TAMs are attracted to and retained in avascular and necrotic areas, where they are exposed to tumor hypoxia. At these sites, TAMs appear to undergo marked phenotypic changes with activation of hypoxia-inducible transcription factors, dramatically upregulating the expression of a large number of genes encoding mitogenic, proangiogenic and prometastatic cytokines and enzymes. As a consequence, high TAMs density has been correlated with increased tumor growth and angiogenesis in various tumor types. Since hypoxia is a hallmark feature of malignant tumors and hypoxic tumor cells are relatively resistant to radio-and chemotherapy, these areas have become a target for novel forms of anticancer therapy. These include hypoxiatargeted gene therapy in which macrophages are armed with therapeutic genes that are activated by hypoxia-responsive promoter elements. This restricts transgene expression to hypoxic areas, where the gene product is then released and acts on neighboring hypoxic tumor cells or proliferating blood vessels. In this way, the responses of macrophages to tumor hypoxia can be exploited to deliver potent antitumor agents to these poorly vascularized, and thus largely inaccessible, areas of tumors. ' 2005 Wiley-Liss, Inc.

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The Regulation of Interleukin-8 by Hypoxia in Human Macrophages—A Potential Role in the Pathogenesis of the Acute Respiratory Distress Syndrome (ARDS)

Cited by 98 publications

References 55 publications

Effects of obstructive sleep apnea on circulating ICAM-1, IL-8, and MCP-1

Effects of obstructive sleep apnea on circulating ICAM-1, IL-8, and MCP-1

Regulation of monocyte chemoattractant protein 1 (MCP-1) release by explants of human visceral adipose tissue

Macrophage migration and gene expression in response to tumor hypoxia

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