Kinetics of proinflammatory cytokines after intraperitoneal injection of tribromoethanol and a tribromoethanol/xylazine combination in ICR mice

Cho, Yoon Ju; Lee, Young Ah; Lee, Jae Won; Kim, Jong In; Han, Jin Soo

doi:10.5625/lar.2011.27.3.197

Cited by 11 publications

(7 citation statements)

References 35 publications

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“…In previous studies where IL‐6 was continuously infused into mice using the same methods, IL‐6 levels in saline pump mice were not reported (43). We hypothesize that the mild elevation in IL‐6 in the mice with a saline pump was due to one of several possibilities: 1 ) an inflammatory response to the subcutaneous infusion pump, 2) a stress response to the glucose tolerance test performed just before death, or 3) a rise due to the effects of tribromoethanol used for euthanasia (44). Therefore, the saline pump mice may have had mildly elevated IL‐6 throughout the study or only in response to terminal procedures.…”

Section: Discussionmentioning

confidence: 99%

Interleukin 6 protects pancreatic β cells from apoptosis by stimulation of autophagy

et al. 2017

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IL-6 is a pleiotropic cytokine with complex roles in inflammation and metabolic disease. The role of IL-6 as a pro- or anti-inflammatory cytokine is still unclear. Within the pancreatic islet, IL-6 stimulates secretion of the prosurvival incretin hormone glucagon-like peptide 1 (GLP-1) by α cells and acts directly on β cells to stimulate insulin secretion Uncovering physiologic mechanisms promoting β-cell survival under conditions of inflammation and stress can identify important pathways for diabetes prevention and treatment. Given the established role of GLP-1 in promoting β-cell survival, we hypothesized that IL-6 may also directly protect β cells from apoptosis. Herein, we show that IL-6 robustly activates signal transducer and activator of transcription 3 (STAT3), a transcription factor that is involved in autophagy. IL-6 stimulates LC3 conversion and autophagosome formation in cultured β cells. IL-6 infusion stimulates a robust increase in lysosomes in the pancreas that is restricted to the islet. Autophagy is critical for β-cell homeostasis, particularly under conditions of stress and increased insulin demand. The stimulation of autophagy by IL-6 is regulated multiple complementary mechanisms including inhibition of mammalian target of rapamycin complex 1 (mTORC1) and activation of Akt, ultimately leading to increases in autophagy enzyme production. Pretreatment with IL-6 renders β cells resistant to apoptosis induced by proinflammatory cytokines, and inhibition of autophagy with chloroquine prevents the ability of IL-6 to protect from apoptosis. Importantly, we find that IL-6 can activate STAT3 and the autophagy enzyme GABARAPL1 in human islets. We also see evidence of decreased IL-6 pathway signaling in islets from donors with type 2 diabetes. On the basis of our results, we propose direct stimulation of autophagy as a novel mechanism for IL-6-mediated protection of β cells from stress-induced apoptosis.-Linnemann, A. K., Blumer, J., Marasco, M. R., Battiola, T. J., Umhoefer, H. M., Han, J. Y., Lamming, D. W., Davis, D. B. Interleukin 6 protects pancreatic β cells from apoptosis by stimulation of autophagy.

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Section: Discussionmentioning

confidence: 99%

Interleukin 6 protects pancreatic β cells from apoptosis by stimulation of autophagy

et al. 2017

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“…What might be the underlying pathophysiological mechanisms? Anesthesia is known to influence cytokine expression in humans, but actually appears to have an anti-inflammatory effect as, for instance, suggested by reduction of circulating Il6 levels [ 7 - 9 ]. The intranasal infection procedure appears to be a more likely candidate.…”

Section: Discussionmentioning

confidence: 99%

Infection- and procedure-dependent effects on pulmonary gene expression in the early phase of influenza A virus infection in mice

et al. 2013

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BackgroundInvestigating the host response in the early stage of influenza A virus (IAV) infection is of considerable interest. However, it is conceivable that effects due to the anesthesia and/or intranasal infection procedure might introduce artifacts. We therefore aimed to evaluate the effects of anesthesia and/or intranasal infection on transcription of selected pulmonary mRNAs in two inbred mouse strains with differential susceptibility to IAV infection.ResultsDBA/2J and C57BL/6J mice were evaluated in a time course experiment in which lung tissue was sampled after 6, 12, 18, 24, 48 and 120 h. After anesthesia with ketamine and xylazine, a suspension of mouse-adapted IAV strain PR8_Mun in 20 μl sterile buffer, or 20 μl sterile buffer only, was instilled intranasally. The mice receiving anesthesia and PBS only were designated the “mock treatment” group. Pulmonary expression of 10 host mRNAs (Fos, Retnla, Irg1, Il6, Il1b, Cxcl10, Stat1, Ifng, Ifnl2, and Mx1) and viral hemagglutinin (HA) mRNA were determined at the designated time points. As expected, weight loss and viral replication were greater in the DBA/2J strain (which is more susceptible to IAV infection). Four mRNAs (Retnla, Irg1, Il6, and Cxcl10) were procedure-dependently regulated in DBA/2J mice between 6 and 24 h, and two (Retnla and Il6) in C57BL/6J mice, although to a lesser extent. All 10 mRNAs rose after infection, but one (Fos) only in DBA/2J mice. These infection-dependent effects could be separated from procedure-dependent effects beginning around 12 h in DBA/2J and 18 h in C57BL/6J mice. The interferon-related mRNAs Stat1, Ifng, Infl2, and Mx1 were unaffected by mock treatment in either mouse strain. Mx1 and Infl2 correlated best with HA mRNA expression (r = 0.97 and 0.93, respectively, in DBA/2J).ConclusionsThese results demonstrate effects of the anesthesia and/or intranasal infection procedure on pulmonary gene expression, which are detectable between approximately 6 and 24 h post procedure and vary in intensity and temporal evolution depending on the mouse strain used. Mock infection controls should be included in all studies on pulmonary gene expression in the early phase of infection with IAV and, likely, other respiratory pathogens.

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“…In fact, in the case of injection of pregnant dams, such adverse effects may be expected to be even worse, including direct harm to the fetus. In addition, other disadvantages such as splenic trauma, serosal hemorrhage, and contamination have been reported [24]. Hence, s.c. injection may represent a more suitable route of administration when dealing with pregnant mice.…”

Section: Discussionmentioning

confidence: 99%

Effects of Subcutaneous LPS Injection on Gestational Length and Intrauterine and Neonatal Mortality in Mice

Lopez

Steinbusch²,

Rutten³

et al. 2015

Neuroimmunomodulation

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Background: Infection during pregnancy can predispose offspring to develop various psychiatric disorders such as depression in later life. In order to investigate the potential mechanisms underlying these associations, animal models of maternal infection have been employed. As such, lipopolysaccharide (LPS) has been commonly used to mimic a bacterial infection in pregnant mice. Objective: The original aim of our study was to investigate the effects of different doses of subcutaneous LPS administration on affective behavior in adult mouse offspring. In the present paper, however, we report that subcutaneous LPS administration has a profound impact on gestational length, litter size, and perinatal mortality in the offspring, even at a relatively low dose. Methods: Pregnant mice were randomly divided into 3 groups, receiving either a high (2 mg/kg) or a low (0.5 mg/kg) dose of LPS or phosphate-buffered saline by means of subcutaneous injection. Subsequently, the effects on gestational length, litter size, and perinatal mortality in the offspring were assessed. Results: After subcutaneous injection with a high dose of LPS, we observed a significant decrease in gestational length and an increase in neonatal mortality. When the low dose was administered, a tendency towards a reduced litter size was observed, most likely reflecting increased intrauterine mortality in response to prenatal maternal LPS exposure. Conclusions: We showed that subcutaneous administration of 2 mg/kg LPS to pregnant mice in the last phase of gestation should be avoided because of high offspring mortality rates, whereas subcutaneous injection of 0.5 mg/kg LPS seems to result in reabsorption of the fetuses.

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Kinetics of proinflammatory cytokines after intraperitoneal injection of tribromoethanol and a tribromoethanol/xylazine combination in ICR mice

Cited by 11 publications

References 35 publications

Interleukin 6 protects pancreatic β cells from apoptosis by stimulation of autophagy

Interleukin 6 protects pancreatic β cells from apoptosis by stimulation of autophagy

Infection- and procedure-dependent effects on pulmonary gene expression in the early phase of influenza A virus infection in mice

Effects of Subcutaneous LPS Injection on Gestational Length and Intrauterine and Neonatal Mortality in Mice

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