Chinchu Jagadan Ushakumari

Boston University

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Qiong Zhou

Chinese Academy of Medical Sciences & Peking Union Medical College

Sijia Na

Xi'an Jiaotong University

Max K. Kroll

Boston University

Cindy Y. Zhou

Boston University

Michael C. Rigor

Boston University

Benjamin D. Lin

Boston University

Mohind C. Mohan

Cochin University of Science and Technology

Yuhua Wang

First Affiliated Hospital of Jiangxi Medical College

B. Prakash Kumar

Sri Venkateswara Veterinary University

Zhen Jiang

Soochow University

Cooperative Institutions

Boston University

Nanchang University

Mahatma Gandhi University

Sree Chitra Thirunal Institute for Medical Sciences and Technology

Chinese Academy of Medical Sciences & Peking Union Medical College

Kunming Medical University

Uniformed Services University of the Health Sciences

Children's National

Hangzhou Children's Hospital

Fu Wai Hospital

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Downregulation of adipogenic genes in 3T3-L1 Pre adipocytes- a possible mechanism of anti-obesity activity of herbal decoction Varanadi Kashayam

Journal of Herbal Medicine (2019)

Chinchu Jagadan Ushakumari Mohind C. Mohan B. Prakash Kumar

Oil Red O

3T3-L1

Lipid droplet

Nile red

10.1016/j.hermed.2019.100309

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Neutrophil Elastase Increases Vascular Permeability and Leukocyte Transmigration in Cultured Endothelial Cells and Obese Mice

Cells (2022)

Chinchu Jagadan Ushakumari Qiong Zhou Yuhua Wang Sijia Na Michael C. Rigor

Neutrophil elastase (NE) plays a pivotal role in inflammation. However, the mechanism underlying NE-mediated inflammation in obesity remains unclear. Here, we report that NE activates protease-activated receptor-2 (PAR2), stimulates actin filament (F-actin) formation, decreases intercellular junction molecule VE-cadherin expression, and increases the permeability of human arterial endothelial cells (hECs). NE also prompts degradation of VE-cadherin and its binding proteins p120- and β-catenins via MG132-sensitive proteasomes. NE stimulates phosphorylation of myosin light-chain (MLC) and its regulator myosin phosphatase target subunit-1 (MYPT1), a target of Rho kinase (ROCK). Inhibitors of PAR2 and ROCK prohibit NE-induced F-actin formation, MLC phosphorylation, and VE-cadherin reduction in hECs, and impede monocyte transmigration through hEC monolayer pretreated with either neutrophils or NE. Further, administration of an NE inhibitor GW311616A significantly attenuates vascular leakage, leukocyte infiltration, and the expression of proinflammatory cytokines in the white adipose tissue from high-fat diet (HFD)-induced obese mice. Likewise, NE-deficient mice are resistant to HFD-induced vascular leakage in the heart. Together, NE regulates actomyosin cytoskeleton activity and VE-cadherin expression by activating PAR2 signaling in the endothelial cells, leading to increased vascular permeability and leukocyte extravasation. Hence, inhibition of NE is a potential approach to mitigate vascular injury and leukocyte infiltration in obesity-related systemic inflammation.

MG132

Vascular permeability

Proinflammatory cytokine

Myosin-light-chain phosphatase

10.3390/cells11152288

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Citations (22)