LIPOCALIN-2 Is a Major Acute-Phase Protein in a Rat and Mouse Model of Sterile Abscess

Sultan, Sadaf; Pascucci, Matteo; Ahmad, Shakil; Malik, Ihtzaz Ahmad; Bianchi, Alberto; Ramadori, Pierluigi; Ahmad, Gulfam; Ramadori, Giuliano

doi:10.1097/shk.0b013e31823918c2

Cited by 51 publications

(55 citation statements)

References 23 publications

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“…From the observation of the slightly elevated number of circulating white blood cells and the indications of kidney injury in wild-type animals exposed to hypoxia, we expected an inflammatory response. The investigation of the renal expression of several proinflammatory cytokines (e.g., TNF-␣ and IL-6), chemokines (e.g., MCP1 and MIP2), and the acute phase protein SAA, which have been previously shown to be increased after induction of AKI and to mediate ischemic AKI (2,51,53), confirmed the hypothesis that only in wild-type mice does hypoxia induce an inflammatory response. Among profibrotic changes, which are inducible by KIM1, it has been also shown that KIM1 expression correlates with MCP1 expression (26).…”

Section: Influence Of Systemic Hypoxia On Clinical and Laboratory Parmentioning

confidence: 59%

Morg1 heterozygous deficiency ameliorates hypoxia-induced acute renal injury

Loeffler

Wolf

2015

American Journal of Physiology-Renal Physiology

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Acute kidney injury is a common complication of critically ill patients and may occur as a result of various factors and coexisting previous illnesses. Some pathophysiological responses seen in critical illness can be similar to the human physiological response to extreme environmental challenges, such as hypoxia from reduced oxygen availability at high altitudes (systemic hypoxia). Due to oxygen deficiency, mammalian cells activate the transcriptional factor hypoxia-inducible factor (HIF); its degradation is regulated by prolyl hydroxylase 3 (PHD3) in interaction with the scaffold protein MAPK organizer 1 (Morg1). While homozygous Morg1(-/-) mice are embryonically lethal, the kidneys of heterozygous Morg1(+/-) mice reveal elevated HIF protein levels and increased serum erythropoietin compared with wild-type Morg1(+/+) mice. In this study, we exposed wild-type and Morg1(+/-) mice to 10% oxygen in a hypoxic chamber for 3 days. This reduced oxygen concentration leads to a deterioration of renal function, an increase in renal inflammation, and significantly more tubular damage and apoptosis in the kidneys of wild-type (Morg1(+/+)) mice. In sharp contrast, Morg1(+/-) kidneys were protected against systemic hypoxia. They show significantly less renal lesions, reduced or no inflammation, and less tubular damage and apoptosis. Thus short-term systemic and subsequently renal hypoxia which may occur in many patients in the intensive care unit induces in wild-type mice renal injury, which is ameliorated by Morg1 deficiency. Our findings suggest that therapeutical manipulation of Morg1 may be an interesting novel target to prevent hypoxia-associated renal damage.

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Section: Influence Of Systemic Hypoxia On Clinical and Laboratory Parmentioning

confidence: 59%

Morg1 heterozygous deficiency ameliorates hypoxia-induced acute renal injury

Loeffler

Wolf

2015

American Journal of Physiology-Renal Physiology

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“…The first two are synthesized during differentiation of neutrophilic granulocytes and stored in specific granules that can be released upon activation [42, 48]. LCN2 has recently been reported to be a major APP in rat and mouse, as mRNA levels dramatically increase in both leukocytes and liver following inflammation [46, 49, 50]. In the current study, LCN2 mRNA was modestly up-regulated (3-fold), suggesting that this gene should be considered a minor APP in caprine leukocytes.…”

Section: Discussionmentioning

confidence: 99%

Activation of innate immune genes in caprine blood leukocytes after systemic endotoxin challenge

et al. 2016

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BackgroundSepsis is a serious health problem associated with a range of infectious diseases in animals and humans. Early events of this syndrome can be mimicked by experimental administration of lipopolysaccharides (LPS). Compared with mice, small ruminants and humans are highly sensitive to LPS, making goats valuable in inflammatory models. We performed a longitudinal study in eight Norwegian dairy goats that received LPS (0.1 μg/kg, Escherichia coli O26:B6) intravenously. A control group of five goats received corresponding volumes of sterile saline. Clinical examinations were performed continuously, and blood samples were collected throughout the trial.ResultsCharacteristic signs of acute sepsis, such as sickness behavior, fever, and leukopenia were observed within 1 h of LPS administration. A high-throughput longitudinal gene expression analysis of circulating leukocytes was performed, and genes associated with the acute phase response, type I interferon signaling, LPS cascade and apoptosis, in addition to cytokines and chemokines were targeted. Pro-inflammatory genes, such as IL1B, CCL3 and IL8, were significantly up-regulated. Interestingly, increased mRNA levels of seven interferon stimulated genes (ISGs) were observed peaking at 2 h, corroborating the increasing evidence that ISGs respond immediately to bacterial endotoxins. A slower response was manifested by four extrahepatic acute phase proteins (APP) (SAA3, HP, LF and LCN2) reaching maximum levels at 5 h.ConclusionsWe report an immediate induction of ISGs in leukocytes in response to LPS supporting a link between the interferon system and defense against bacterial infections. The extrahepatic expression of APPs suggests that leukocytes contribute to synthesis of these proteins at the beginning of a systemic inflammation. Taken together, these findings provide insights into the dynamic regulation of innate immune genes, as well as raising new questions regarding the importance of ISGs and extrahepatic APPs in leukocytes after systemic endotoxin challenge.Electronic supplementary materialThe online version of this article (doi:10.1186/s12917-016-0870-x) contains supplementary material, which is available to authorized users.

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“…Monoclonal anti-LCN2 antibody, NBPI-05182, (Novus Biologicals) [61] Liver tissue NBP1-05182 (Acris GmbH) [70] Liver tissue Monoclonal anti-LCN2 (Novus Biologicals) [56] Human Urine MAB1757 (R&D Systems) [68] Immuno(fluorescence) staining Mouse Liver tissue Not commercially available antibody [64] Liver tissue AF1857 (R&D Systems)…”

Section: Western Blot Mousementioning

confidence: 99%

“…Not commercially available antibody [46] Rat Liver tissue AF3508 (R&D Systems) [52] Liver tissue AF350 (R&D Systems) [52] Liver tissue Goat polyclonal anti-LCN2 (R&D Systems) [56] Liver tissue Monoclonal anti-LCN2 antibody, NBPI-5182 (Novus Biologicals) [61] ELISA † Mouse Blood serum Mouse LCN2 ELISA-DuoSet Development Kit (R&D Systems) [64] Blood serum Lipocalin-2/NGAL ELISA kit (BioVendor) [49] Rat Blood serum Lipocalin-2 ELISA Bioporto Diagnostics Kit 046 (Bioporto Diagnostics) [56,70] Blood serum ELISA Kit-046 (BioPorto Diagnostics) [61] Human Urine NGAL ELISA kit (BioPorto Diagnostics) [68] Blood serum Human LCN2 ELISA Kit (R&D Systems) [64] Blood serum Lipocalin-2/NGAL ELISA kit (BioVendor) [49] Blood serum Human Lipocalin-2/NGAL Duoset kit (R&D Systems)…”

Section: Western Blot Mousementioning

confidence: 99%