The Alarmin, Interleukin-33, Increases Vascular Tone via Extracellular Signal Regulated Kinase-Mediated Ca2+ Sensitization and Endothelial Nitric Oxide Synthase Inhibition

Details

• Personal Author:
  Batchelor T ; Bowdridge E ; DeVallance E ; Garner K ; Goldsmith WT ; Griffith J ; Hussain S ; Kelley EE ; Nurkiewicz TR ; Seman M ; Velayutham M
• Description:
  Alarmins are classified by their release from damaged or ruptured cells. Many alarmins have been found to increase vascular tone and oppose endothelium-dependent dilatation (EDD). Interleukin (IL)-33 plays a prominent role in lung injury and can be released during vascular injury and in chronic studies found to be cardioprotective. Our recent work has implicated IL-33 in acute vascular dysfunction following inhalation of engineered nanomaterials (ENM). However, the mechanisms linking IL-33 to vascular tone have not been interrogated. We therefore aimed to determine whether IL-33 directly influenced microvascular tone and endothelial function. Isolated feed arteries and in vivo arterioles from male and female Sprague-Dawley rats were used to determine direct vascular actions of IL-33. Mesenteric feed arteries and arterioles demonstrated reduced intraluminal diameters when treated with increasing concentrations of recombinant IL-33. IL-33 activated extracellular signal regulated kinase (ERK)1/2 of rat aortic smooth muscle cells but not phosphorylation of myosin light chain kinase. This suggested IL-33 may sensitize arterioles to Ca2+-mediated responses. Indeed, IL-33 augmented the myogenic- and phenylephrine-induced vasoconstriction. Additionally, incubation of arterioles with 1 ng IL-33 attenuated ACh-mediated EDD. Mechanistically, in human aortic endothelial cells, we demonstrate that IL-33-mediated ERK1/2 activation leads to inhibitory phosphorylation of serine 602 on endothelial nitric oxide synthase. Finally, we demonstrate that IL-33-ERK1/2 contributes to vascular tone following two known inducers of IL-33; ENM inhalation and the rupture endothelial cells. The present study provides novel evidence that IL-33 increases vascular tone via canonical ERK1/2 activation in microvascular smooth muscle and endothelium. Altogether, it is suggested IL-33 plays a critical role in microvascular homeostasis following barrier cell injury. [Description provided by NIOSH]
• Subjects:
  Immune System Lung Occupational Health Respiratory System Safety
• Keywords:
  Author Keywords: Endothelial Function Cell Damage Cell Signaling Endothelial Cells ERK Signaling Immune Reaction Inhalation Interleukin Lung Tissue Nanomaterials Smooth Muscle Constristion Vascular Tone

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• ISSN:
  0022-3751
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Philadelphia Region [OSHA] ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  602
• Issue:
  22
• NIOSHTIC Number:
  nn:20070305
• Citation:
  J Physiol 2024 Nov; 602(22):6087-6107
• Contact Point Address:
  T. R. Nurkiewicz: West Virginia University School of Medicine, Department of Physiology, Pharmacology, & Toxicology, 3051 Health Sciences Centre North, 64 Medical Centre Dr, Morgantown, WV 26505
• Email:
  tnurkiewicz@hsc.wvu.edu
• Federal Fiscal Year:
  2025
• Performing Organization:
  West Virginia University
• Peer Reviewed:
  True
• Start Date:
  20220901
• Source Full Name:
  The Journal of Physiology
• End Date:
  20230831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:1349e18d3cb0c5564306f95d575526411a852f52ce87c275c1580d3441cbc0dafa56471294c639d4126ae1ca305b663367e35312449a5d6d801e9c75b245bc7e
• Download URL:
  https://stacks.cdc.gov/view/cdc/208544/cdc_208544_DS1.pdf
• File Type:
  [PDF - 2.18 MB ]