Leptin Downregulates LPS-Induced Lung Injury: Role of Corticosterone and Insulin

Landgraf, Maristella de Almeida; Silva, Reinaldo Correia; Corrêa-Costa, Matheus; Hiyane, Meire Ioshie; Carvalho, Maria Helena Catelli de; Landgraf, Richardt Gama; Câmara, Niels Olsen Saraiva

doi:10.1159/000358656

Cited by 33 publications

(33 citation statements)

References 52 publications

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“…This mitochondrial dysfunction is only corrected by normoglycemia, but that was not our model's focus. In our study, the dose of insulin used [7][8] was not sufficient to ameliorate renal function maybe because the toxic glucose concentration persisted after insulin treatment, causing an overload in the renal cortex and mitochondrial malfunction, which culminates with organ dysfunction [29,30].…”

Section: Cellular Physiology and Biochemistrymentioning

confidence: 67%

Insulin Modulates Liver Function in a Type I Diabetes Rat Model

Nolasco¹,

Zanoni²,

Nunes³

et al. 2015

Cell Physiol Biochem

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Background/Aims: Several studies have been performed to unravel the association between diabetes and increased susceptibility to infection. This study aimed to investigate the effect of insulin on the local environment after cecal ligation and puncture (CLP) in rats. Methods: Diabetic (alloxan, 42 mg/kg i.v., 10 days) and non-diabetic (control) male Wistar rats were subjected to a two-puncture CLP procedure and 6 h later, the following analyses were performed: (a) total and differential cell counts in peritoneal lavage (PeL) and bronchoalveolar lavage (BAL) fluids; (b) quantification of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-10 and cytokine-induced neutrophil chemoattractant (CINC)-1 and CINC-2 in the PeL and BAL fluids by enzyme-linked immunosorbent assay (ELISA); (c) total leukocyte count using a veterinary hematology analyzer and differential leukocyte counts on stained slides; (d) biochemical parameters (urea, creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) by colorimetric analyses); and (e) lung, kidney, and liver morphological analyses (hematoxylin and eosin staining). Results: Relative to controls, non-diabetic and diabetic CLP rats exhibited an increased in the concentration of IL-1β, IL-6, IL-10, CINC-1, and CINC-2 and total and neutrophil in the PeL fluid. Treatment of these animals with neutral protamine Hagedorn insulin (NPH, 1IU and 4IU, respectively, s.c.), 2 hours before CLP procedure, induced an increase on these cells in the PeL fluid but it did not change cytokine levels. The levels of ALT, AST, ALP, and urea were higher in diabetic CLP rats than in non-diabetic CLP rats. ALP levels were higher in diabetic sham rats than in non-diabetic sham rats. Treatment of diabetic rats with insulin completely restored ALT, AST, and ALP levels. Conclusion: These results together suggest that insulin attenuates liver dysfunction during early two-puncture CLP-induced peritoneal inflammation in diabetic rats.

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Section: Cellular Physiology and Biochemistrymentioning

confidence: 67%

Insulin Modulates Liver Function in a Type I Diabetes Rat Model

Nolasco¹,

Zanoni²,

Nunes³

et al. 2015

Cell Physiol Biochem

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“…Since ALI is characterize by excessive and prolonged activation of neutrophils, which results in basement membrane destruction and permeability increases of the alveolar-capillary barrier [8,9,10,11,12], previous efforts have been focusing on the modulation of the immunity. Specifically, IL-8 is a critical cytokine that is produced and released by neutrophils.…”

Section: Discussionmentioning

confidence: 99%

“…Specifically, IL-8 is a critical cytokine that is produced and released by neutrophils. IL-8 targets microvascular endothelial cells via its receptor CXCR1 and CXCR2 to trigger the changes in permeability of vascular endothelium to facilitate the lung injury [8,9,10,11,12]. Hence, it may be logic that inhibition of CXCR2 in lung endothelial cells may be beneficial.…”

Section: Discussionmentioning

confidence: 99%

“…Excessive and prolonged activation of neutrophils hallmark ALI, resulting in basement membrane destruction and permeability increases of the alveolar-capillary barrier [8,9,10,11,12]. Migrating neutrophils also release pro-inflammatory and pro-apoptotic cytokines, e.g.…”

Section: Introductionmentioning

confidence: 99%

“…Migrating neutrophils also release pro-inflammatory and pro-apoptotic cytokines, e.g. Interleukin 8 (IL-8), to allow the injury progress [8,9,10,11,12]. IL-8 is a potent neutrophil attractant and activator.…”

Section: Introductionmentioning

confidence: 99%

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Cordyceps Militaris Alleviates Severity of Murine Acute Lung Injury Through miRNAs-Mediated CXCR2 Inhibition

Liu

Tang²,

Huang³

et al. 2015

Cell Physiol Biochem

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Background/Aims: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are lethal diseases in humans, and the current treatments have limited therapeutic effects. Cordyceps militaris (CM) is a caterpillar-grown traditional medicinal mushroom, and has been used as a natural invigorant for longevity, endurance, and vitality in China. Recently, purified extracts from CM have been shown to have beneficial effects on various diseases including cancer. Nevertheless, a role of CM in ALI has not been examined previously. Methods: Here, we used a bleomycin-induced ALI model to study the effects of CM on the severity of ALI in mice. The levels of CXCR2, a receptor for Interleukin 8 (IL-8) in pulmonary microvascular endothelial cells, were examined in different experimental groups. The levels of microRNA (miR)-1321 and miR-3188 were also examined in lung samples and in CM. Adeno-associated viruses carrying miR-1321 and miR-3188 were injected into bleomycin-treated mice for evaluation their effects on the severity of ALI. Results: CM treatment significantly alleviated the severity of bleomycin-induced ALI in mice. The increases in lung CXCR2 by bleomycin were significantly reduced by CM at protein level, but not at mRNA level. CM contained high levels of 2 miRNAs (miR-1321 and miR-3188) that target 3'-UTR of CXCR2 mRNA to inhibit its expression. Overexpression of miR-1321 and miR-3188 in mouse lung through AAV-mediated gene therapy mimicked the effects of CM. Conclusion: CM may alleviate severity of murine ALI through miRNAs-mediated CXCR2 inhibition.

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Leptin reduces LPS‐induced A1 reactive astrocyte activation and inflammation via inhibiting p38‐MAPK signaling pathway

Sun,

Song,

et al. 2024

Glia

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Neurotoxic A1 reactive astrocytes are induced by inflammatory stimuli. Leptin has been confirmed to have neuroprotective properties. However, its effect on the activation of A1 astrocytes in infectious inflammation is unclear. In the current study, astrocytes cultured from postnatal day 1 Sprague–Dawley rats were stimulated with lipopolysaccharide (LPS) to induce an acute in vitro inflammatory response. Leptin was applied 6 h later to observe its protective effects. The viability of the astrocytes was assessed. A1 astrocyte activation was determined by analyzing the gene expression of C3, H2‐D1, H2‐T23, and Serping 1 and secretion of pro‐inflammatory cytokines IL‐6 and TNF‐α. The levels of phospho‐p38 (pp38) and nuclear factor‐κB (NF‐κB) phosphor‐p65 (pp65) were measured to explore the possible signaling pathways. Additionally, an LPS‐induced inflammatory animal model was established to investigate the in vivo effects of leptin on A1 astrocytic activation. Results showed that in the in vitro culture system, LPS stimulation caused elevated expression of A1 astrocyte‐specific genes and the secretion of pro‐inflammatory cytokines, indicating the activation of A1 astrocytes. Leptin treatment significantly reversed the LPS induced upregulation in a dose‐dependent manner. Similarly, LPS upregulated pp38, NF‐κB pp65 protein and inflammatory cytokines were successfully reduced by leptin. In the LPS‐induced animal model, the amelioratory effect of leptin on A1 astrocyte activation and inflammation was further confirmed, showed by the reduced sickness behaviors, A1 astrocyte genesis and inflammatory cytokines in vivo. Our results demonstrate that leptin efficiently inhibits LPS‐induced neurotoxic activation of A1 astrocytes and neuroinflammation by suppressing p38‐MAPK signaling pathway.

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Leptin Downregulates LPS-Induced Lung Injury: Role of Corticosterone and Insulin

Cited by 33 publications

References 52 publications

Insulin Modulates Liver Function in a Type I Diabetes Rat Model

Insulin Modulates Liver Function in a Type I Diabetes Rat Model

Cordyceps Militaris Alleviates Severity of Murine Acute Lung Injury Through miRNAs-Mediated CXCR2 Inhibition

Leptin reduces LPS‐induced A1 reactive astrocyte activation and inflammation via inhibiting p38‐MAPK signaling pathway

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