Related Experiment Video
Updated: May 15, 2026
10:16
Visualizing Leukocyte Rolling and Adhesion in Angiotensin II-Infused Mice: Techniques and Pitfalls
Published on: January 4, 2018
Interleukin-17 causes Rho-kinase-mediated endothelial dysfunction and hypertension
Hoanglan Nguyen1, Valorie L Chiasson, Piyali Chatterjee
1Division of Nephrology & Hypertension, Department of Internal Medicine, Texas A&M Health Science Center College of Medicine/Scott & White Memorial Hospital, 702 SW HK Dodgen Loop, Temple, TX 76504, USA.
Cardiovascular Research
|December 25, 2012
Summary
Interleukin-17A (IL-17) elevates blood pressure by impairing endothelial nitric oxide (NO) production via the RhoA/Rho-kinase pathway. Targeting IL-17 or Rho-kinase may offer new hypertension treatments for autoimmune diseases.
Area of Science:
- Cardiovascular Research
- Immunology
- Endothelial Biology
Background:
- Elevated pro-inflammatory cytokine IL-17 is linked to hypertensive autoimmune diseases.
- The specific mechanism connecting IL-17 to hypertension remains unclear.
- This study investigates IL-17's role in endothelial nitric oxide (NO) production and blood pressure regulation.
Purpose of the Study:
- To determine if IL-17 increases blood pressure by reducing endothelial NO production.
- To elucidate the molecular pathway involved in IL-17-induced endothelial dysfunction.
- To explore potential therapeutic targets for IL-17-associated hypertension.
Main Methods:
- Assessed IL-17 effects on endothelial cells, isolated mouse aortas, and live mice.
- Measured eNOS Thr495 phosphorylation, RhoA expression, and NO-dependent relaxation.
- Utilized IL-17 neutralizing antibodies and Rho-kinase inhibitors.
Main Results:
- IL-17 significantly increased inhibitory eNOS Thr495 phosphorylation and RhoA activation in endothelial cells and mouse aortas.
- IL-17 treatment led to hypertension in mice, accompanied by impaired NO-dependent relaxation and increased eNOS Thr495 phosphorylation and RhoA expression.
- Inhibition of Rho-kinase abrogated IL-17-induced endothelial dysfunction and hypertension.
Conclusions:
- IL-17 activates the RhoA/Rho-kinase pathway, causing endothelial dysfunction and hypertension.
- IL-17 and Rho-kinase inhibitors show potential as novel anti-hypertensive therapies for IL-17-associated autoimmune conditions.
Related Concept Videos
01:24T Cell Types and Functions
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
01:24Regulation of Angiogenesis and Blood Supply
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
01:29Hypertension II: Pathophysiology
Hypertension is a chronic condition in which the blood's force against artery walls is excessively high, posing risks such as heart disease. The condition's underlying mechanisms involve complex interactions among the cardiovascular, kidney, and autonomic nervous systems.Renin-Angiotensin-Aldosterone System (RAAS): This system significantly influences blood pressure regulation. When blood pressure decreases, the kidneys secrete renin. This enzyme transforms angiotensinogen, a plasma protein,...
01:24Small GTPases - Ras and Rho
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
01:20The JAK-STAT Signaling Pathway
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
01:25Acute Inflammation III: Local and Systemic Effects
Acute inflammation produces a coordinated set of local and systemic changes that limit injury, eliminate pathogens, and initiate repair. These responses arise within minutes of infection, trauma, or chemical insult and are driven by vascular alterations and leukocyte-derived mediators. When the stimulus resolves, the reaction typically abates within days.Local EffectsAt the site of injury, arteriolar vasodilation increases blood flow, resulting in redness and warmth. Simultaneously, increased...