Hypoxia increases production of interleukin-1 and tumor necrosis factor by human mononuclear cells

Ghezzi, Pietro; Dinarello, Charles A.; Bianchi, Marina; Rosandich, Mary; Repine, John E.; White, Carl W.

doi:10.1016/1043-4666(91)90015-6

Cited by 234 publications

(125 citation statements)

References 32 publications

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“…1). Interestingly, yet consistent with our previous reports (18,31), IL-1a was upregulated under hypoxia, as indicated by mRNA transcripts and protein levels (Fig. 1B).…”

Section: Resultssupporting

confidence: 80%

IL-1α and IL-1β Recruit Different Myeloid Cells and Promote Different Stages of Sterile Inflammation

Rider

Carmi

Guttman

et al. 2011

The Journal of Immunology

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465

368

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The immune system has evolved to protect the host from invading pathogens and to maintain tissue homeostasis. Although the inflammatory process involving pathogens is well documented, the intrinsic compounds that initiate sterile inflammation and how its progression is mediated are still not clear. Because tissue injury is usually associated with ischemia and the accompanied hypoxia, the microenvironment of various pathologies involves anaerobic metabolites and products of necrotic cells. In the current study, we assessed in a comparative manner the role of IL-1α and IL-1β in the initiation and propagation of sterile inflammation induced by products of hypoxic cells. We found that following hypoxia, the precursor form of IL-1α, and not IL-1β, is upregulated and subsequently released from dying cells. Using an inflammation-monitoring system consisting of Matrigel mixed with supernatants of hypoxic cells, we noted accumulation of IL-1α in the initial phase, which correlated with the infiltration of neutrophils, and the expression of IL-1β correlated with later migration of macrophages. In addition, we were able to show that IL-1 molecules from cells transfected with either precursor IL-1α or mature IL-1β can recruit neutrophils or macrophages, respectively. Taken together, these data suggest that IL-1α, released from dying cells, initiates sterile inflammation by inducing recruitment of neutrophils, whereas IL-1β promotes the recruitment and retention of macrophages. Overall, our data provide new insight into the biology of IL-1 molecules as well as on the regulation of sterile inflammation.

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“…1). Interestingly, yet consistent with our previous reports (18,31), IL-1a was upregulated under hypoxia, as indicated by mRNA transcripts and protein levels (Fig. 1B).…”

Section: Resultssupporting

confidence: 80%

IL-1α and IL-1β Recruit Different Myeloid Cells and Promote Different Stages of Sterile Inflammation

Rider

Carmi

Guttman

et al. 2011

The Journal of Immunology

Self Cite

465

368

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“…Prolonged hypoxia appears to activate the inflammation system, determined from elevated concentrations of inflammatory mediators (55,56). The association between hypoxia, inflammation and oxidative stress is in accordance with the hypothesis that inflammatory diseases are associated with oxidative stress and elevated levels of oxidative damage to DNA and lipids.…”

Section: Biological Plausibilitysupporting

confidence: 54%

Hypoxia and oxidation levels of DNA and lipids in humans and animal experimental models

et al. 2008

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SummaryThe objective of this review was to evaluate the association between hypoxia and oxidative damage to DNA and lipids. Evaluation criteria encompassed specificity and validation status of the biomarkers, study design, strength of the association, dose-response relationship, biological plausibility, analogous exposures, and effect modification by intervention. The collective interpretation indicates persuasive evidence from the studies in humans for an association between hypoxia and elevated levels of oxidative damage to DNA and lipids. The levels of oxidatively generated DNA lesions and lipid peroxidation products depend on both the duration and severity of the exposure to hypoxia. Largest effects are observed with exposure to hypoxia at high altitude, but other factors, including ultraviolet light, exercise, exertion, and low intake of antioxidants, might contribute to the effect observed in subjects at high altitude. Most of the animal experimental models should be interpreted with caution because the assays for assessment of lipid peroxidation products have suboptimal validity.2008 IUBMB IUBMB Life, 60(11): 707-723, 2008

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“…2,5,9 The which microthrombus formation stimulates cytokine production is not fully understood. Ghezzi et al 34 and Koga et al 16 activation of the coagulation system could be inhibited by APC, UTM, or DEGR-Xa, and might possibly contribute to showed that hypoxia markedly increased the production of IL-1 by monocytes. Jones et al 35 reported that thrombin and attenuating the cytokine production in the pathological process of ischemia/reperfusion injury of the liver.…”

Section: Methodsmentioning

confidence: 99%

Pretreatment with activated protein C or active human urinary thrombomodulin attenuates the production of cytokine-induced neutrophil chemoattractant following ischemia/reperfusion in rat liver

et al. 1997

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bance induced by microthrombotic occlusion following We investigated the role of anticoagulant in the isischemia/reperfusion. (HEPATOLOGY 1997;25:1136-1140.) chemia/reperfusion injury of the liver, using activated protein C (APC), active human urinary thrombomodulin (UTM), and factor Xa blocked at the active site Endothelial cells play an important regulatory role in the (DEGR-Xa). Liver ischemia was induced in male Wistar coagulation system. Protein C is a vitamin K-dependent rats by occlusion of the portal vein with a microvascuplasma glycoprotein that circulates as an inactive zymogen. lar clip for 30 minutes. Each anticoagulant was injectedAt the endothelial cell surface, thrombin in complex with intravenously 10 minutes before clamping the portal the integral membrane protein, thrombomodulin, converts vein. Serum concentrations of cytokine-induced neuprotein C to its active form by specific cleavage of an activatrophil chemoattractant (CINC) were determined by enzyme-linked immunosorbent assay. The serum levels tion peptide. [1][2][3] The active form of protein C has potent anticoof CINC increased significantly following reperfusion, agulant activity as a feedback regulator of thrombin generareaching a peak in 6 hours, and then decreasing gradu-tion, 4,5 and also has profibrinolytic, 6,7 anti-ischemic, 8 and ally to control levels by 24 hours. CINC levels in rats anti-inflammatory properties. 9 pretreated with APC (500 U/kg), UTM (3,000 TMU/kg), Neutrophil activation has been shown to play an important or DEGR-Xa (10 mg/kg) peaked 3 hours following reper-role in ischemia/reperfusion injury associated with the shock fusion and decreased rapidly to baseline level within process. 10,11 Recently, Jaeschke et al. 12 and Poggeti et al. 13 6 and 12 hours, respectively. These peak values were showed the importance of neutrophils in the development significantly lower than those observed in untreated of liver ischemia/reperfusion injury. When activated in the rats (P õ .01). Expression of CINC transcripts in liver microcirculation, neutrophils release a variety of inflammatissue of untreated rats was evaluated by Northern blot tory mediators capable of producing endothelial cell injury. 14 analysis and peaked 3 hours following reperfusion. Pre-Among these mediators, granulocyte proteases and hydrogen treatment with these anticoagulants significantly de-peroxide have been shown to induce inactivation of thrombocreased the expression of CINC messenger RNA tran-modulin synergistically, as well as damage to the endothelial scripts as compared with untreated animals. cell integrity. 15 Thus, it is likely that microthrombus can be Myeloperoxidase activity and the number of neutro-formed in ischemia/reperfusion as a result of activated leukophils accumulated into the liver 24 hours following cyte-induced endothelial cell injury, which may lead to tissue ischemia/reperfusion were also significantly decreased ischemia. Because production of interleukin (IL)-1 by monoin animals pretreated with these anticoagulants. In ad-cyte...

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Hypoxia increases production of interleukin-1 and tumor necrosis factor by human mononuclear cells

Cited by 234 publications

References 32 publications

IL-1α and IL-1β Recruit Different Myeloid Cells and Promote Different Stages of Sterile Inflammation

IL-1α and IL-1β Recruit Different Myeloid Cells and Promote Different Stages of Sterile Inflammation

Hypoxia and oxidation levels of DNA and lipids in humans and animal experimental models

Pretreatment with activated protein C or active human urinary thrombomodulin attenuates the production of cytokine-induced neutrophil chemoattractant following ischemia/reperfusion in rat liver

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