Ghrelin protects musculocutaneous tissue from ischemic necrosis by improving microvascular perfusion

2012 ◽  
Vol 302 (3) ◽  
pp. H603-H610 ◽  
Author(s):  
F. Rezaeian ◽  
R. Wettstein ◽  
C. Scheuer ◽  
K. Bäumker ◽  
A. Bächle ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Nuclear Factor Κb ◽  
Capillary Density ◽  
Capillary Perfusion ◽  
Ischemic Necrosis ◽  
Dorsal Skinfold Chamber ◽  
Tissue Protection ◽  
Wound Breakdown ◽  
Oxide Synthase

Persistent ischemia in musculocutaneous tissue may lead to wound breakdown and necrosis. The objective of this experimental study was to analyze, whether the gastric peptide ghrelin prevents musculocutaneous tissue from necrosis and to elucidate underlying mechanisms. Thirty-two C57BL/6 mice equipped with a dorsal skinfold chamber containing ischemic musculocutaneous tissue were allocated to four groups: 1) ghrelin; 2) Nω-nitro-l-arginine methyl ester (l-NAME); 3) ghrelin and l-NAME; and 4) control. Microcirculation, inflammation, angiogenesis, and tissue survival were assessed by fluorescence microscopy. Inducible and endothelial nitric oxide synthase (iNOS I and eNOS), vascular endothelial growth factor (VEGF), as well as nuclear factor κB (NF-κB) were assessed by Western blot analysis. Ghrelin-treated animals showed an increased expression of iNOS and eNOS in critically perfused tissue compared with controls. This was associated with arteriolar dilation, increased arteriolar perfusion, and a sustained functional capillary density. Ghrelin further upregulated NF-κB and VEGF and induced angiogenesis. Finally, ghrelin reduced microvascular leukocyte-endothelial cell interactions, apoptosis, and overall tissue necrosis ( P < 0.05 vs. control). Inhibition of nitric oxide by l-NAME did not affect the anti-inflammatory and angiogenic action of ghrelin but completely blunted the ghrelin-induced tissue protection by abrogating the arteriolar dilation, the improved capillary perfusion, and the increased tissue survival. Ghrelin prevents critically perfused tissue from ischemic necrosis. Tissue protection is the result of a nitric oxide synthase-mediated improvement of the microcirculation but not due to induction of angiogenesis or attenuation of inflammation. This might represent a promising, noninvasive, and clinically applicable approach to protect musculocutaneous tissue from ischemia.

scholarly journals Activation of Nuclear Factor κB and Induction of Inducible Nitric Oxide Synthase by Ureaplasma urealyticumin Macrophages

2000 ◽  
Vol 68 (12) ◽  
pp. 7087-7093 ◽  
Author(s):  
Y.-H. Li ◽  
Z.-Q. Yan ◽  
J. Skov Jensen ◽  
K. Tullus ◽  
A. Brauner
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Alveolar Macrophages ◽  
Nuclear Factor Κb ◽  
Inos Expression ◽  
Dependent Manner ◽  
Nuclear Factor ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

ABSTRACT Chronic lung disease (CLD) of prematurity is an inflammatory disease with a multifactorial etiology. The importance ofUreaplasma urealyticum in the development of CLD is debated, and steroids produce some improvement in neonates with this disease. In the present study, the capability of U. urealyticum to stimulate rat alveolar macrophages to produce nitric oxide (NO), express inducible nitric oxide synthase (iNOS), and activate nuclear factor κB (NF-κB) in vitro was characterized. The effect of NO on the growth of U. urealyticum was also investigated. In addition, the impact of dexamethasone and budesonide on these processes was examined. We found that U. urealyticum antigen (≥4 × 107 color-changing units/ml) stimulated alveolar macrophages to produce NO in a dose- and time-dependent manner (P < 0.05). This effect was further enhanced by gamma interferon (100 IU/ml; P < 0.05) but was attenuated by budesonide and dexamethasone (10−4 to 10−6 M) (P < 0.05). The mRNA and protein levels of iNOS were also induced in response to U. urealyticum and inhibited by steroids.U. urealyticum antigen triggered NF-κB activation, a possible mechanism for the induced iNOS expression, which also was inhibited by steroids. NO induced by U. urealyticum caused a sixfold reduction of its own growth after infection for 10 h. Our findings imply that U. urealyticum may be an important factor in the development of CLD. The host defense response againstU. urealyticum infection may also be influenced by NO. The down-regulatory effect of steroids on NF-κB activation, iNOS expression, and NO production might partly explain the beneficial effect of steroids in neonates with CLD.

scholarly journals Hyaluronan Fragments Induce Nitric-oxide Synthase in Murine Macrophages through a Nuclear Factor κB-dependent Mechanism

1997 ◽  
Vol 272 (12) ◽  
pp. 8013-8018 ◽  
Author(s):  
Charlotte M. McKee ◽  
Charles J. Lowenstein ◽  
Maureen R. Horton ◽  
Jean Wu ◽  
Clare Bao ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Murine Macrophages ◽  
Oxide Synthase ◽  
Dependent Mechanism

scholarly journals Porcine Alveolar Macrophages’ Nitric Oxide Synthase-Mediated Generation of Nitric Oxide Exerts Important Defensive Effects against Glaesserella parasuis Infection

Pathogens ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 234
Author(s):  
Qi Cao ◽  
Huan Wang ◽  
Wenbin Wei ◽  
Yujin Lv ◽  
Zhao Wen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Alveolar Macrophage ◽  
Alveolar Macrophages ◽  
Nuclear Factor Κb ◽  
Porcine Alveolar Macrophage ◽  
No Production ◽  
Cytokines And Chemokines ◽  
Direct Demonstration ◽  
Oxide Synthase

Glaesserella parasuis is a habitual bacterium of pigs’ upper respiratory tracts. Its infection initiates with the invasion and colonization of the lower respiratory tracts of pigs, and develops as the bacteria survive host pulmonary defenses and clearance by alveolar macrophages. Alveolar macrophage-derived nitric oxide (NO) is recognized as an important mediator that exerts antimicrobial activity as well as immunomodulatory effects. In this study, we investigated the effects and the signaling pathway of NO generation in porcine alveolar macrophages 3D4/21 during G. parasuis infection. We demonstrated a time and dose-dependent generation of NO in 3D4/21 cells by G. parasuis, and showed that NO production required bacterial viability and nitric oxide synthase 2 upregulation, which was largely contributed by G. parasuis-induced nuclear factor-κB signaling’s activation. Moreover, the porcine alveolar macrophage-derived NO exhibited prominent bacteriostatic effects against G. parasuis and positive host immunomodulation effects by inducing the production of cytokines and chemokines during infection. G. parasuis in turn, selectively upregulated several nitrate reductase genes to better survive this NO stress, revealing a battle of wits during the bacteria–host interactions. To our knowledge, this is the first direct demonstration of NO production and its anti-infection effects in alveolar macrophages with G. parasuis infection.

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