Role of interleukin-6 in murine airway responses to ozone

2005 ◽  
Vol 288 (2) ◽  
pp. L390-L397 ◽  
Author(s):  
Richard A. Johnston ◽  
Igor N. Schwartzman ◽  
Lesley Flynt ◽  
Stephanie A. Shore
Keyword(s):  
Interleukin 6 ◽  
Lavage Fluid ◽  
Whole Body ◽  
High Dose ◽  
Outcome Indicators ◽  
Airway Injury ◽  
Inflammatory Protein ◽  
Airway Responses ◽  
Whole Body Plethysmography

This study sought to examine the role of interleukin-6 (IL-6) in ozone (O3)-induced airway injury, inflammation, and hyperresponsiveness (AHR). Subacute (72 h) exposure to 0.3 ppm O3significantly elevated bronchoalveolar lavage fluid (BALF) protein, neutrophils, and soluble TNF receptors (sTNFR1 and sTNFR2) in wild-type C57BL/6 (IL-6+/+) mice; however, all four outcome indicators were significantly reduced in IL-6-deficient (IL-6−/−) compared with IL-6+/+mice. Acute O3exposure (2 ppm for 3 h) increased BALF protein, KC, macrophage inflammatory protein(MIP)-2, eotaxin, sTNFR1, and sTNFR2 in IL-6+/+mice. However, MIP-2 and sTNFR2 were not significantly increased following O3exposure in IL-6−/−mice. Increases in BALF neutrophils induced by O3(2 ppm for 3 h) were also significantly reduced in IL-6−/−vs. IL-6+/+mice. Airway responsiveness to methacholine was measured by whole body plethysmography before and following acute (3 h) or subacute (72 h) exposure to 0.3 ppm O3. Acute O3exposure caused AHR in both groups of mice, but there was no genotype-related difference in the magnitude of O3-induced AHR. AHR was absent in mice of either genotype exposed for 72 h. Our results indicate that IL-6 deficiency reduces airway neutrophilia, as well as the levels of BALF sTNFR1 and sTNFR2 following acute high dose and/or subacute low-dose O3exposure, but has no effect on O3-induced AHR.

scholarly journals Activation of Astrocytes in the Persistence of Post-hypoxic Respiratory Augmentation

2021 ◽  
Vol 12 ◽  
Author(s):  
Isato Fukushi ◽  
Kotaro Takeda ◽  
Mieczyslaw Pokorski ◽  
Yosuke Kono ◽  
Masashi Yoshizawa ◽  
...  
Keyword(s):  
Acute Hypoxia ◽  
Whole Body ◽  
High Dose ◽  
Ventilatory Responses ◽  
Adult Mice ◽  
Term Potentiation ◽  
Before And After ◽  
Whole Body Plethysmography ◽  
Hypoxic Gas Mixture

Acute hypoxia increases ventilation. After cessation of hypoxia loading, ventilation decreases but remains above the pre-exposure baseline level for a time. However, the mechanism of this post-hypoxic persistent respiratory augmentation (PHRA), which is a short-term potentiation of breathing, has not been elucidated. We aimed to test the hypothesis that astrocytes are involved in PHRA. To this end, we investigated hypoxic ventilatory responses by whole-body plethysmography in unanesthetized adult mice. The animals breathed room air, hypoxic gas mixture (7% O2, 93% N2) for 2min, and again room air for 10min before and after i.p. administration of low (100mg/kg) and high (300mg/kg) doses of arundic acid (AA), an astrocyte inhibitor. AA suppressed PHRA, with the high dose decreasing ventilation below the pre-hypoxic level. Further, we investigated the role of the astrocytic TRPA1 channel, a putative ventilatory hypoxia sensor, in PHRA using astrocyte-specific Trpa1 knockout (asTrpa1−/−) and floxed Trpa1 (Trpa1f/f) mice. In both Trpa1f/f and asTrpa1−/− mice, PHRA was noticeable, indicating that the astrocyte TRPA1 channel was not directly involved in PHRA. Taken together, these results indicate that astrocytes mediate the PHRA by mechanisms other than TRPA1 channels that are engaged in hypoxia sensing.

Aerosolized deferoxamine prevents lung and systemic injury caused by smoke inhalation

1994 ◽  
Vol 77 (5) ◽  
pp. 2057-2064 ◽  
Author(s):  
C. LaLonde ◽  
K. Ikegami ◽  
R. Demling
Keyword(s):  
Antioxidant Properties ◽  
Lipid Peroxides ◽  
Lavage Fluid ◽  
Smoke Inhalation ◽  
Iron Release ◽  
Histological Changes ◽  
Airway Injury ◽  
Mucosal Edema ◽  
Protein Rich

We assessed the role of oxidant release at the airway mucosal surface on airway injury and systemic response to a severe smoke insult. Adult sheep (n = 20) were insufflated with well-characterized smoke from burning cotton toweling. A standardized dose of 12 breaths of smoke with a tidal volume of 20 ml/kg was given under anesthesia. Sheep were awakened, monitored for 24 h, and killed; data were compared with control sheep. Sheep were given 1) humidified oxygen, 2) continuous aerosol of 10% deferoxamine (DFO)-pentastarch solution beginning after smoke, 3) DFO-alone aerosol, or 4) pentastarch-alone aerosol. DFO has antioxidant properties directly and chelates iron. Severe respiratory failure occurred in all but DFO-pentastarch group. Shunt fraction increased from a control of 4%. Histological assessment revealed severe airway mucosal edema, ulceration, bronchorrhea, and severe atelectasis but only moderate alveolar edema. Increased lipid peroxides were also noted in free airway fluid and in bronchoalveolar lavage fluid. In addition, oxygen consumption increased by 75%, fluid requirements increased threefold, and protein-rich systemic soft tissue lymph flow doubled, all significant increases compared with control sheep. No significant physiological or histological changes were noted in DFO-pentastarch aerosol group. We conclude that 1) oxidants possibly initiated through free iron release are involved in severe smoke-induced airway injury and resulting systemic inflammatory response, probably through an amplified oxidant injury and 2) an aerosol of a DFO-pentastarch complex prevents the injury process, whereas DFO alone is not effective as an aerosol.

Macrophage-specific metalloelastase (MMP-12) truncates and inactivates ELR+ CXC chemokines and generates CCL2, -7, -8, and -13 antagonists: potential role of the macrophage in terminating polymorphonuclear leukocyte influx

Blood ◽  
2008 ◽  
Vol 112 (8) ◽  
pp. 3455-3464 ◽  
Author(s):  
Richard A. Dean ◽  
Jennifer H. Cox ◽  
Caroline L. Bellac ◽  
Alain Doucet ◽  
Amanda E. Starr ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Lavage Fluid ◽  
Binding Motif ◽  
Wild Type ◽  
Lps Challenge ◽  
Inflammatory Protein ◽  
Leukocyte Influx ◽  
Cc Chemokines ◽  
Intranasal Instillation

AbstractThrough the activity of macrophage-specific matrix metalloproteinase-12 (MMP-12), we found that macrophages dampen the lipopolysaccharide (LPS)-induced influx of polymorphonuclear leukocytes (PMNs)—thus providing a new mechanism for the termination of PMN recruitment in acute inflammation. MMP-12 specifically cleaves human ELR+ CXC chemokines (CXCL1, -2, -3, -5, and -8) at E-LR, the critical receptor-binding motif or, for CXCL6, carboxyl-terminal to it. Murine (m) MMP-12 also cleaves mCXCL1, -2, and -3 at E-LR. MMP-12-cleaved mCXCL2 (macrophage-inflammatory protein-2 [MIP-2]) and mCXCL3 (dendritic cell inflammatory protein-1 [DCIP-1]) lost chemotactic activity. Furthermore, MMP-12 processed and inactivated monocyte chemotactic proteins CCL2, -7, -8, and -13 at position 4-5 generating CCR antagonists. Indeed, PMNs and macrophages in bronchoalveolar lavage fluid were significantly increased 72 hours after intranasal instillation of LPS in Mmp12−/− mice compared with wild type. Specificity occurred at 2 levels. Macrophage MMP-1 and MMP-9 did not cleave in the ELR motif. Second, unlike human ELR+CXC chemokines, mCXCL5 (LPS-induced CXC chemokine [LIX]) was not inactivated. Rather, mMMP-12 cleavage at Ser4-Val5 activated the chemokine, promoting enhanced PMN early infiltration in wild-type mice compared with Mmp12−/− mice 8 hours after LPS challenge in air pouches. We propose that the macrophage, specifically through MMP-12, assists in orchestrating the regulation of acute inflammatory responses by precise proteolysis of ELR+CXC and CC chemokines.

scholarly journals The “birth of death”: MRI step-by-step reveals the early appearance of a bone marrow infarct

2019 ◽  
Vol 8 (3) ◽  
pp. 205846011983469 ◽  
Author(s):  
Elie Barakat ◽  
Nathalie Guischer ◽  
Frédéric Houssiau ◽  
Frederic E. Lecouvet
Keyword(s):  
Bone Marrow ◽  
De Novo ◽  
Whole Body ◽  
High Signal ◽  
Systemic Steroid ◽  
High Dose ◽  
Mr Images ◽  
Whole Body Mri ◽  
Skeletal Involvement

The magnetic resonance imaging (MRI) appearance of an “established” bone marrow infarct is well-known, consisting of an area of preserved bone marrow signal surrounded by a serpiginous line. We report the uncommon observation of the very early phases of appearance of a bone marrow infarct, showing its progressive de novo appearance on MR images paralleling clinical symptoms and high-dose systemic steroid administration in a young female patient, presenting with acute knee pain. The initial knee MR examination performed one week after pain onset showed no abnormality. One week later, a second examination showed subtle ill-defined dotted signal abnormalities of the bone marrow of uncertain significance, of high signal on PDFS sequences. A third MR study obtained again one week later showed more evident findings with confluence of the high signal “dots” into a serpiginous line with a geographical appearance of the lesion, corresponding to the typical MRI presentation of bone marrow infarcts. Follow-up MRI at seven weeks showed definitive stability of this bone marrow infarct. A whole-body MRI performed for whole skeleton screening revealed multiple bone marrow infarcts typical for systemic avascular necrosis. This case represents a novel observation of the “birth” of a bone marrow infarct, from early intriguing changes to its typical ring-shaped appearance on MR images. It also reminds of the key role of MRI for early diagnosis of bone marrow infarcts and illustrates the emerging role of whole-body MRI for the detection of multifocal, asymptomatic skeletal involvement by ischemic lesions in systemic osteonecrosis.

Role of interleukin-1β, interleukin-6 and macrophage inflammatory protein-1β in prostaglandin-E2-induced hyperthermia in rats

Life Sciences ◽  
1996 ◽  
Vol 59 (12) ◽  
pp. PL185-PL190 ◽  
Author(s):  
A. Fernández-Alonso ◽  
K. Benamar ◽  
M. SancibriÁn ◽  
F.J. López-Valpuesta ◽  
F.J. Mifiano
Keyword(s):  
Prostaglandin E2 ◽  
Interleukin 6 ◽  
Interleukin 1Β ◽  
Induced Hyperthermia ◽  
Inflammatory Protein ◽  
Macrophage Inflammatory Protein

scholarly journals Role of whole body plethysmogRaphy in pRactice of geneRal pRactitioneR

2012 ◽  
Vol 5 (2) ◽  
pp. 40-47
Author(s):  
Rustem I. shaymuRatov ◽  
◽  
olga yu. mIkhopaRova ◽  
elvIRa B. FRolova ◽  
◽  
...  
Keyword(s):  
General Practitioner ◽  
Whole Body ◽  
Body Plethysmography ◽  
Whole Body Plethysmography

Attenuation of Lung Inflammation by Adrenergic Agonists in Murine Acute Lung Injury

2001 ◽  
Vol 95 (4) ◽  
pp. 947-953 ◽  
Author(s):  
Vinay K. Dhingra ◽  
Ari Uusaro ◽  
Cheryl L. Holmes ◽  
Keith R. Walley
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Interleukin 6 ◽  
Lavage Fluid ◽  
Lung Lavage ◽  
Adrenergic Agonists ◽  
Beta Adrenergic ◽  
Beta Adrenergic Agonists ◽  
Inflammatory Protein

Background Acute lung injury leading to a systemic inflammatory response greatly increases mortality in critically ill patients. Cardiovascular management of these patients frequently involves beta-adrenergic agonists. These agents may alter the inflammatory response. Therefore, the authors tested the hypothesis that beta-adrenergic agonists alter the pulmonary inflammatory response during acute lung injury in mice. Methods Five-week-old CD-1 mice received continuous infusions of 10 microg x kg(-1) x min(-1) dobutamine, 6 microg x kg(-1) x min(-1) dopexamine, or vehicle via intraperitoneal mini osmotic pumps, followed immediately by intratracheal instillation of approximately 2 microg/kg endotoxin (or phosphate-buffered saline control). Six hours later the mice were killed, and lung lavage was performed. Interleukin-6 and -10 concentrations in lung homogenates were measured using enzyme-linked immunosorbent assay. Interleukin-6 and macrophage inflammatory protein-2 mRNA was measured using reverse-transcription polymerase chain reaction. Results Interleukin-6 protein and mRNA significantly increased after intratracheal endotoxin (P < 0.001), and the fraction of neutrophils in lung lavage fluid increased in endotoxin-treated (41 +/- 25%) versus control mice (2 +/- 4%, P < 0.05). Treatment of endotoxic mice with dobutamine significantly decreased interleukin-6 protein (P < 0.05) and mRNA (P < 0.05) expression. Dopexamine had similar but less pronounced effects. Dobutamine decreased interleukin-10 expression, whereas dopexamine did not. In endotoxemic mice, both dobutamine and dopexamine decreased induction of macrophage inflammatory protein-2 mRNA (P < 0.05) and reduced the fraction of neutrophils in lung lavage fluid (P < 0.05). Conclusions In endotoxin-induced acute lung injury, beta-adrenergic agonists can significantly decrease proinflammatory cytokine expression, decrease induction of chemokine mRNA, and decrease the resultant neutrophil infiltrate in the lung.

Role of alveolar macrophage and migrating neutrophils in hemorrhage-induced priming for ALI subsequent to septic challenge

2006 ◽  
Vol 290 (1) ◽  
pp. L51-L58 ◽  
Author(s):  
Joanne Lomas-Neira ◽  
Chun-Shiang Chung ◽  
Mario Perl ◽  
Stephen Gregory ◽  
Walter Biffl ◽  
...  
Keyword(s):  
Lung Injury ◽  
Lung Tissue ◽  
Peripheral Blood ◽  
Lavage Fluid ◽  
Tissue Samples ◽  
Relative Contribution ◽  
Inflammatory Protein ◽  
Tnf Α ◽  
Pulmonary Macrophages

Acute lung injury (ALI) is identified with the targeting/sequestration of polymorphonuclear leukocytes (PMN) to the lung. Instrumental to PMN targeting are chemokines [e.g., macrophage inflammatory protein-2 (MIP-2), keratinocyte-derived chemokine (KC), etc.] produced by macrophage, PMN, and other resident pulmonary cells. However, the relative contribution of resident pulmonary macrophages as opposed to PMN in inducing ALI is poorly understood. We therefore hypothesize that depletion of peripheral blood PMN and/or the oblation of a macrophage-mediated PMN chemokine signal (via macrophage deficiency) will reduce the inflammation and ALI observed in mice following hemorrhage (Hem) and subsequent sepsis (CLP) in our murine model of ALI. To examine this we pretreated mice with either 500 μg anti-mouse Gr1 antibody/animal (to deplete PMN) or subjected mice deficient in mature macrophage (B6C3Fe-a/a-CsF1op) to Hem (90 min at 35 ± 5 mmHg) followed by resuscitation. Twenty-four hours post-Hem, mice were subjected to CLP and killed 24 h later, and lung tissue samples were collected. Our data showed that in the absence of either peripheral blood PMN or mature tissue macrophages there was a suppression of IL-6, KC, and MIP-2 levels in lung tissue from Hem/CLP mice as well as a reduction in PMN influx to the lung and lung injury (bronchoalveolar lavage fluid protein). In contrast, lung tissue IL-10 and TNF-α levels were suppressed in the macrophage-deficient Hem/CLP mice compared with PMN-depleted Hem/CLP mice. Together, these data suggest that both the PMN and the macrophage are required to induce inflammation seen here, however, macrophage not PMN regulate the release of IL-10, independent of local changes in TNF.

Role of nitric oxide in regulation of long-term pressure-natriuresis relationship in Dahl rats

1995 ◽  
Vol 268 (6) ◽  
pp. H2375-H2383 ◽  
Author(s):  
L. Hu ◽  
R. D. Manning
Keyword(s):  
Nitric Oxide ◽  
Arterial Pressure ◽  
Whole Body ◽  
High Dose ◽  
No Production ◽  
High Sodium ◽  
Induced Hypertension ◽  
Pressure Natriuresis

The aim of this study was to determine the role of nitric oxide (NO) in the development of salt-induced hypertension in the Brookhaven strain of Dahl rats. Six- to seven-week-old conscious salt-sensitive (S) and salt-resistant (R) rats with indwelling arterial and venous catheters received low-, normal-, and high-sodium intakes sequentially over a 16-day period, and L-arginine was infused intravenously at 2 or 4 mg.kg-1.min-1 over this time. The S rats had an impaired NO production as evidenced by a decreased urinary nitrate plus nitrite excretion. The administration of the low or high dose of L-arginine increased the whole body NO production of the S rats to that of the control R rats, and the high dose of L-arginine prevented the shift of long-term pressure-natriuresis relationship, the elevation of arterial pressure, and the increase in salt sensitivity of arterial pressure in the S rats. The sodium and water balances were not different between the age-matched R and S rats. In conclusion, a continuous infusion of L-arginine prevented both the changes in the pressure-natriuresis relationship and the development of salt-induced hypertension in Dahl S rats.

scholarly journals Interleukin-6 Expression by Hypothalamic Microglia in Multiple Inflammatory Contexts: A Systematic Review

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Vanessa C. D. Bobbo ◽  
Carlos P. Jara ◽  
Natália F. Mendes ◽  
Joseane Morari ◽  
Lício A. Velloso ◽  
...  
Keyword(s):  
Systematic Review ◽  
Interleukin 6 ◽  
Energy Homeostasis ◽  
Metabolic Diseases ◽  
Whole Body ◽  
Positive Energy ◽  
Anatomical Site ◽  
Control Food ◽  
Control Food Intake

Interleukin-6 (IL-6) is a unique cytokine that can play both pro- and anti-inflammatory roles depending on the anatomical site and conditions under which it has been induced. Specific neurons of the hypothalamus provide important signals to control food intake and energy expenditure. In individuals with obesity, a microglia-dependent inflammatory response damages the neural circuits responsible for maintaining whole-body energy homeostasis, resulting in a positive energy balance. However, little is known about the role of IL-6 in the regulation of hypothalamic microglia. In this systematic review, we asked what types of conditions and stimuli could modulate microglial IL-6 expression in murine model. We searched the PubMed and Web of Science databases and analyzed 13 articles that evaluated diverse contexts and study models focused on IL-6 expression and microglia activation, including the effects of stress, hypoxia, infection, neonatal overfeeding and nicotine exposure, lipopolysaccharide stimulus, hormones, exercise protocols, and aging. The results presented in this review emphasized the role of “injury-like” stimuli, under which IL-6 acts as a proinflammatory cytokine, concomitant with marked microglial activation, which drive hypothalamic neuroinflammation. Emerging evidence indicates an important correlation of basal IL-6 levels and microglial function with the maintenance of hypothalamic homeostasis. Advances in our understanding of these different contexts will lead to the development of more specific pharmacological approaches for the management of acute and chronic conditions, like obesity and metabolic diseases, without disturbing the homeostatic functions of IL-6 and microglia in the hypothalamus.

Sign in / Sign up

Export Citation Format

Share Document