Synthetic RGDS peptide attenuates lipopolysaccharide-induced pulmonary inflammation by inhibiting integrin signaled MAP kinase pathways

Moon, Changsuk; Han, Jeong Ran; Park, Hyun-Jung; Hah, Jong Sik; Kang, Jihee Lee

doi:10.1186/1465-9921-10-18

Cited by 60 publications

(55 citation statements)

References 48 publications

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“…25 In fact, a 5 b 1 integrin blockage using RGDS peptides prevents lung damage induced by LPS. 26 On the other hand, targeting of ADAM10 led to incomplete cell migration in vitro and in vivo as seen by an arrest of migrating cells in the chemotaxis membranes and within the lung tissue. Combining these 2 observations, it can be speculated that the reduced adhesion to matrix components such as fibronectin hinders cell migration and thereby prolongs the migration time through the chemotaxis membranes, through the endothelium, and through interstitial lung tissue, similar to the observed inhibition by RGDS peptides.…”

Section: Discussionmentioning

confidence: 99%

“…Combining these 2 observations, it can be speculated that the reduced adhesion to matrix components such as fibronectin hinders cell migration and thereby prolongs the migration time through the chemotaxis membranes, through the endothelium, and through interstitial lung tissue, similar to the observed inhibition by RGDS peptides. 26 Therefore, fewer cells would have completed migration, whereas the majority would still be in the progress of migration. Thus, ADAM10 deficiency leads to accumulation of slow-migrating cells in the chemotaxis membranes and interstitial accumulation within the lung.…”

Section: Discussionmentioning

confidence: 99%

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Leukocytes require ADAM10 but not ADAM17 for their migration and inflammatory recruitment into the alveolar space

Pruessmeyer

Hess

Alert

et al. 2014

Blood

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Key Points• ADAM10 but not ADAM17 on leukocytes is essential for chemokine-induced signaling, adhesion, cytoskeletal rearrangement, and migration.• Leukocyte-expressed ADAM10 promotes leukocyte recruitment and edema formation in a murine model of acute pulmonary inflammation.Inflammation is a key process in various diseases, characterized by leukocyte recruitment to the inflammatory site. This study investigates the role of a disintegrin and a metalloproteinase (ADAM) 10 and ADAM17 for leukocyte migration in vitro and in a murine model of acute pulmonary inflammation. Inhibition experiments or RNA knockdown indicated that monocytic THP-1 cells and primary human neutrophils require ADAM10 but not ADAM17 for efficient chemokine-induced cell migration. Signaling and adhesion events that are linked to cell migration such as p38 and r GTPase-family activation, F-actin polymerization, adhesion to fibronectin, and upregulation of a 5 integrin were also dependent on ADAM10 but not ADAM17. This was confirmed with leukocytes isolated from mice lacking either ADAM10 or ADAM17 in all hematopoietic cells (vav 1 guanine nucleotide exchange factor [Vav]-Adam10 2/2 or Vav-Adam17 2/2 mice). In lipopolysaccharide-induced acute pulmonary inflammation, alveolar recruitment of neutrophils and monocytes was transiently increased in Vav-Adam17 2/2 but steadily reduced in Vav-Adam10 2/2 mice. This deficit in alveolar leukocyte recruitment was also observed in LysM-Adam10 2/2 mice lacking ADAM10in myeloid cells and correlated with protection against edema formation. Thus, with regard to leukocyte migration, leukocyteexpressed ADAM10 but not ADAM17 displays proinflammatory activities and may therefore serve as a target to limit inflammatory cell recruitment. (Blood. 2014;123(26):4077-4088)

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Leukocytes require ADAM10 but not ADAM17 for their migration and inflammatory recruitment into the alveolar space

Pruessmeyer

Hess

Alert

et al. 2014

Blood

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“…Therefore, targeting neutrophil integrin αvβ3 with its ligand, RGDSK (peptide or RNT), might block free available integrin αvβ3 receptors that may inhibit its transmigration across endothelial cells ( Figure 7B). This suggestion was recently 34 However, RNTs and cyclic peptides are not comparable due to differences in their physical and chemical dimensions, which might have contributed to the different trend in our mouse model. We previously reported a P38 mitogenactivated protein kinase-dependent proinflammatory response of K 90 /RGDSK 10 -RNT while the role of P38 mitogenactivated protein kinase in transmigration of neutrophils and lung inflammation is well documented.…”

mentioning

confidence: 81%

“…We previously reported a P38 mitogenactivated protein kinase-dependent proinflammatory response of K 90 /RGDSK 10 -RNT while the role of P38 mitogenactivated protein kinase in transmigration of neutrophils and lung inflammation is well documented. 16,[34][35][36] Based on these reports we propose that K 90 /RGDSK 10 -RNT might trigger a P38 mitogen-activated protein kinase cascade in vivo that upregulates the proinflammatory response ( Figure 7C). …”

mentioning

confidence: 83%

RGD-tagged helical rosette nanotubes aggravate acute lipopolysaccharide-induced lung inflammation

Suri¹,

Mills²,

Aulakh³

et al. 2011

IJN

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Rosette nanotubes (RNT) are a novel class of self-assembled biocompatible nanotubes that offer a built-in strategy for engineering structure and function through covalent tagging of synthetic self-assembling modules (G∧C motif). In this report, the G∧C motif was tagged with peptide Arg-Gly-Asp-Ser-Lys (RGDSK-G∧C) and amino acid Lys (K-G∧C) which, upon co-assembly, generate RNTs featuring RGDSK and K on their surface in predefined molar ratios. These hybrid RNTs, referred to as K x /RGDSK y -RNT, where x and y refer to the molar ratios of K-G∧C and RGDSK–G∧C, were designed to target neutrophil integrins. A mouse model was used to investigate the effects of intravenous K x /RGDSK y -RNT on acute lipopolysaccharide (LPS)-induced lung inflammation. Healthy male C57BL/6 mice were treated intranasally with Escherichia coli LPS 80 μg and/or intravenously with K 90 /RGDSK 10 -RNT. Here we provide the first evidence that intravenous administration of K 90 /RGDSK 10 -RNT aggravates the proinflammatory effect of LPS in the mouse. LPS and K 90 /RGDSK 10 -RNT treatment groups showed significantly increased infiltration of polymorphonuclear cells in bronchoalveolar lavage fluid at all time points compared with the saline control. The combined effect of LPS and K 90 /RGDSK 10 -RNT was more pronounced than LPS alone, as shown by a significant increase in the expression of interleukin-1β, MCP-1, MIP-1, and KC-1 in the bronchoalveolar lavage fluid and myeloperoxidase activity in the lung tissues. We conclude that K 90 /RGDSK 10 -RNT promotes acute lung inflammation, and when used along with LPS, leads to exaggerated immune response in the lung.

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“…The molecular mechanisms responsible for alterations of ALI have been extensively studied and a number of signaling pathways, including the JAK/STAT (3,4), PI3 kinase/Akt (5,6) and mitogen-activated protein kinase pathways (7)(8)(9), have been demonstrated to be important under a number of conditions.…”

Section: Introductionmentioning

confidence: 99%

Upregulation of Shh and Ptc1 in hyperoxia‑induced acute lung injury in neonatal rats

et al. 2012

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Abstract. The aim of the present study was to observe the expression of sonic hedgehog (Shh) and Ptc signaling molecules in the lungs of newborn rats exposed to prolonged hyperoxia, and to explore the role of the SHH signaling pathway in hyperoxia-induced lung injury. Newborn Sprague-Dawley rat pups were placed in chambers containing room air or oxygen above 95% for 14 days following birth. The rats were sacrificed after 3, 7 or 14 days and their lungs were removed. Sections were fixed and subjected to hematoxylin and eosin (H&E) staining. Shh and Ptc1 were quantitated by immunohistochemistry. The total RNA and protein were also extracted from lung tissue; realtime PCR (RT-PCR) and western blot analysis were utilized to assess the mRNA and protein expression of Shh and Ptc1. H&E staining demonstrated significant histomorphological changes in the hyperoxia-exposed lungs at 3, 7 and 14 days of age. The results of the immunohistochemistry, RT-PCR and western blot analysis demonstrated that the expression of Shh was significantly higher in the hyperoxia-exposed lungs at 3, 7 and 14 days, while Ptc1 was significantly elevated at 7 and 14 days. Exposure of the neonatal rat lung to prolonged hyperoxia resulted in acute lung injury and histomorphological changes. Shh and Ptc1 were upregulated in a time-dependent manner in the course of hyperoxia-induced lung injury. The SHH signal pathway may be involved in the pathogenesis of hyperoxia-induced lung injury. This is the first evidence that in vivo hyperoxia induces activation of the SHH signal transduction pathway in newborn lung. IntroductionAs an important therapeutic intervention, high supplemental oxygen concentrations are often administered to neonates with respiratory diseases, including hyaline membrane disease, persistent pulmonary hypertension and others. High concentrations of oxygen are known to cause acute lung injury (ALI) and bronchopulmonary dysplasia (BPD). Prolonged exposure to hyperoxia can also result in severe epithelial and endothelial damage (1). Oxidative stress plays a role in the pathogenesis of ALI. Despite major advances in our understanding of the mechanisms leading to ALI, this condition remains a problem.Lung alveolar interstitial fibroblasts and their communication with adjacent epithelial cells are important in lung development and injury/repair (2). The molecular mechanisms responsible for alterations of ALI have been extensively studied and a number of signaling pathways, including the JAK/STAT (3,4), PI3 kinase/Akt (5,6) and mitogen-activated protein kinase pathways (7-9), have been demonstrated to be important under a number of conditions.The SHH signaling pathway consists chiefly of Shh, Ptc1, Smo, Gli1, Gli2 and Gli3 molecules. It has long been recognized that this pathway is essential for embryonic development, and has been revealed to regulate cell migration, proliferation and apoptosis (10). This cascade is crucial for the patterning of early lung morphogenesis (11). However, its role in acute lung injury/repair remains to be dete...

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Synthetic RGDS peptide attenuates lipopolysaccharide-induced pulmonary inflammation by inhibiting integrin signaled MAP kinase pathways

Cited by 60 publications

References 48 publications

Leukocytes require ADAM10 but not ADAM17 for their migration and inflammatory recruitment into the alveolar space

Leukocytes require ADAM10 but not ADAM17 for their migration and inflammatory recruitment into the alveolar space

RGD-tagged helical rosette nanotubes aggravate acute lipopolysaccharide-induced lung inflammation

Upregulation of Shh and Ptc1 in hyperoxia‑induced acute lung injury in neonatal rats

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