scholarly journals A peptide derived from chaperonin 60.1, IRL201104, inhibits LPS-induced acute lung inflammation

2021 ◽  
Author(s):  
Francis Man ◽  
Suchita Nadkarni ◽  
Varsha Kanabar ◽  
Rodrigo e-Lacerda ◽  
Sueli Gomes Ferreira ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Lung Inflammation ◽  
Umbilical Vein ◽  
Neutrophil Migration ◽  
Human Neutrophils ◽  
Integrin Expression ◽  
Annexin A1 ◽  
Adhesion Molecule Expression ◽  
Acute Lung Inflammation ◽  
Anti Inflammatory

Chaperonin 60.1 (Cpn60.1) is a protein derived from M. tuberculosis that has been shown, along with its peptide fragment IRL201104, to have beneficial effects in models of allergic inflammation. To further investigate the anti-inflammatory properties of Cpn60.1 and IRL201104, we have investigated these molecules in a model of non-allergic lung inflammation. Mice were treated with Cpn60.1 (0.5-5000ng/kg) or IRL201104 (0.00025-2.5ng/kg), immediately before intranasal instillation of bacterial lipopolysaccharide (LPS). Cytokine levels and cell numbers in mouse bronchoalveolar lavage (BAL) fluid were measured 4h after LPS administration. In some experiments mice were depleted of lung-resident phagocytes. Cells from BAL fluid were analysed for inflammasome function. Human umbilical vein endothelial cells (HUVEC) were analysed for adhesion molecule expression. Human neutrophils were analysed for integrin expression, chemotaxis and cell polarisation. Cpn60.1 and IRL201104 significantly inhibited neutrophil migration into the airways, independently of route of administration. This effect of the peptide was absent in TLR4 and Annexin A1 knock-out mice. Intravital microscopy revealed that IRL201104 reduced leukocyte adhesion and migration into inflamed tissues. However, IRL201104 did not significantly affect adhesion molecule expression in HUVEC or integrin expression, chemotaxis or polarisation of human neutrophils at the studied concentrations. In phagocyte-depleted animals, the anti-inflammatory effect of IRL201104 was not significant. IRL201104 significantly reduced IL-1β and NLRP3 expression and increased A20 expression in BAL cells. This study shows that Cpn60.1 and IRL201104 potently inhibit LPS-induced neutrophil infiltration in mouse lungs by a mechanism dependent on tissue-resident phagocytes and to a much lesser extent the pro-resolving factor Annexin A1.

scholarly journals Pulmonary Endothelial Protein Kinase C-Delta (PKCδ) Regulates Neutrophil Migration in Acute Lung Inflammation

2014 ◽  
Vol 184 (1) ◽  
pp. 200-213 ◽  
Author(s):  
Mark J. Mondrinos ◽  
Ting Zhang ◽  
Shuang Sun ◽  
Paul A. Kennedy ◽  
Devon J. King ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Lung Inflammation ◽  
Neutrophil Migration ◽  
Acute Lung Inflammation ◽  
Protein Kinase C Delta ◽  
Kinase C

Adenosine inhibits cytokine release and expression of adhesion molecules by activated human endothelial cells

1996 ◽  
Vol 270 (2) ◽  
pp. C522-C529 ◽  
Author(s):  
M. G. Bouma ◽  
F. A. van den Wildenberg ◽  
W. A. Buurman
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Vascular Endothelium ◽  
Cell Activation ◽  
Umbilical Vein ◽  
Intercellular Adhesion Molecule ◽  
Cytokine Release ◽  
Adenosine Deaminase Activity ◽  
Anti Inflammatory

Ischemia induces excessive ATP catabolism with subsequent local release of its metabolite adenosine, an autacoid with anti-inflammatory properties. Because activation of the vascular endothelium is critical to the inflammatory host response during ischemia and reperfusion, the effects of adenosine on two major determinants of endothelial cell activation (i.e., the release of proinflammatory cytokines and the expression of adhesion molecules) were studied. Adenosine dose dependently inhibited the release of interleukin (IL)-6 and IL-8 by stimulated human umbilical vein endothelial cells (HUVEC). Expression of E-selectin and vascular cell adhesion molecule 1 (VCAM-1), but not intercellular adhesion molecule 1 (ICAM-1), by activated HUVEC was also reduced by adenosine. Inhibition of endogenous adenosine deaminase activity by erythro-9-(2-hydroxy-3-nonyl)adenine or 2'-deoxycoformycin strongly enhanced the inhibitory effects of exogenous adenosine on cytokine release and expression of E-selectin and VCAM-1. However, a clear role for specific adenosine receptors in the described inhibitory events could not be established. Together, these data imply that the vascular endothelium constitutes an important target for the anti-inflammatory actions of adenosine.

Effect of hyperoxia on adhesion molecule expression in human endothelial cells and neutrophils

1997 ◽  
Vol 272 (3) ◽  
pp. L418-L425 ◽  
Author(s):  
Y. Suzuki ◽  
T. Aoki ◽  
O. Takeuchi ◽  
K. Nishio ◽  
K. Suzuki ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecule ◽  
Umbilical Vein ◽  
Oxygen Toxicity ◽  
Intercellular Adhesion Molecule ◽  
Adhesion Molecule Expression ◽  
Neutrophil Accumulation ◽  
Protein Kinase C Inhibitor ◽  
Human Pulmonary Artery ◽  
Umbilical Vein Endothelial Cells

To investigate the pathogenesis of pulmonary oxygen toxicity, we examined the effect of hyperoxia on adhesion molecule expression in cultured human pulmonary artery endothelial cells (HPAEC) and human umbilical vein endothelial cells (HUVEC). Endothelial cell monolayers were exposed to either hyperoxic (90% O(2)-5% CO(2)) or normoxic (21% O(2)-5% CO(2)) conditions for various periods. The level of intercellular adhesion molecule (ICAM)-1 expression had increased in hyperoxia-exposed HPAEC and HUVEC at 48 h (194 +/- 38 and 233 +/- 56%, respectively; P < 0.001) and at 72 h (200 +/- 43 and 223 +/- 52%, respectively; P < 0.001) compared with normoxic conditions. These hyperoxia-induced ICAM-1 expressions were dose dependently attenuated by a protein kinase C inhibitor (H-7). In contrast, the levels of P-selectin and E-selectin expression in HPAEC and HUVEC were unchanged. The levels of ICAM-1 mRNA and the numbers of adherent neutrophils were increased in HPAEC and HUVEC at 48 and 72 h of hyperoxia. On the other hand, hyperoxia caused neutrophil H(2)O(2) production without affecting the level of CD11/CD18 expression. These results suggest that increased ICAM-1 expression in endothelial cells plays an important role in neutrophil accumulation during hyperoxia.

scholarly journals Anti-inflammatory role of PGD2 in acute lung inflammation and therapeutic application of its signal enhancement

2013 ◽  
Vol 110 (13) ◽  
pp. 5205-5210 ◽  
Author(s):  
T. Murata ◽  
K. Aritake ◽  
Y. Tsubosaka ◽  
T. Maruyama ◽  
T. Nakagawa ◽  
...  
Keyword(s):  
Lung Inflammation ◽  
Signal Enhancement ◽  
Acute Lung Inflammation ◽  
Therapeutic Application ◽  
Anti Inflammatory

Variation of adhesion molecule expression on human umbilical vein endothelial cells upon multiple cytokine application

2002 ◽  
Vol 321 (1-2) ◽  
pp. 11-16 ◽  
Author(s):  
Markus Raab ◽  
Heide Daxecker ◽  
Snezana Markovic ◽  
Alireza Karimi ◽  
Andrea Griesmacher ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecule ◽  
Umbilical Vein ◽  
Adhesion Molecule Expression ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells

scholarly journals Leukocyte-specific protein 1 regulates neutrophil recruitment in acute lung inflammation

2015 ◽  
Vol 309 (9) ◽  
pp. L995-L1008 ◽  
Author(s):  
Nguyen Phuong Khanh Le ◽  
Shankaramurthy Channabasappa ◽  
Mokarram Hossain ◽  
Lixin Liu ◽  
Baljit Singh
Keyword(s):  
Lung Inflammation ◽  
Neutrophil Migration ◽  
Specific Protein ◽  
Neutrophil Recruitment ◽  
Acute Lung Inflammation ◽  
Western Blots ◽  
Monocyte Chemoattractant Protein 1 ◽  
Murine Bone Marrow ◽  
Human Lungs ◽  
Activated Neutrophils

The mechanisms of excessive migration of activated neutrophils into inflamed lungs, credited with tissue damage, are not fully understood. We explored the hitherto unknown expression of leukocyte-specific protein 1 (LSP1) in human and mouse lungs and neutrophils and examined its role in neutrophil migration in acute lung inflammation. Autopsied septic human lungs showed increased LSP1 labeling in epithelium, endothelium, and leukocytes, including in their nuclei compared with normal lungs. We induced acute lung inflammation through intranasal administration of E. coli lipopolysaccharide (LPS) (80 μg) in LSP1-deficient ( Lsp1−/−) and wild-type (WT) 129/SvJ mice. Immunocytochemistry and Western blots showed increased expression of LSP1 and phosphorylated LSP1 in lungs of LPS-treated WT mice. Histology showed more congestion, inflammation, and Gr-1+neutrophils in lung of WT mice than Lsp1−/−mice. LPS-treated WT mice had significantly more neutrophils in bronchoalveolar lavage (BAL) and myeloperoxidase levels in lungs compared with Lsp1−/−mice. However, there were no differences in lung tissue and BAL concentrations of keratinocyte-derived chemokine, monocyte chemoattractant protein-1, macrophage inflammatory protein-1α and -1β, vascular permeability, and phosphorylated p38 MAPK between LPS-treated WT and Lsp1−/−mice, whereas TNF-α concentration was higher in BAL fluid from LPS-treated WT. Immunoelectron microscopy showed increased LSP1 in the nuclei of LPS-treated neutrophils. We also found increased levels of phosphorylated LSP1 associated with plasma membrane, nucleus, and cytosol at various times after LPS treatment of murine bone marrow-derived neutrophils, suggesting its role in modulation of neutrophil cytoskeleton and the membrane. These data collectively show increased expression of LSP1 in inflamed mouse and human lungs and its role in neutrophil recruitment and lung inflammation.

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