Endothelial dysfunction in pulmonary arterial hypertension: loss of cilia length regulation upon cytokine stimulation

Pulmonary Circulation
Anneloes DummerBeerend P Hierck

Abstract

Pulmonary arterial hypertension (PAH) is a syndrome characterized by progressive lung vascular remodelling, endothelial cell (EC) dysfunction, and excessive inflammation. The primary cilium is a sensory antenna that integrates signalling and fine tunes EC responses to various stimuli. Yet, cilia function in the context of deregulated immunity in PAH remains obscure. We hypothesized that cilia function is impaired in ECs from patients with PAH due to their inflammatory status and tested whether cilia length changes in response to cytokines. Primary human pulmonary and mouse embryonic EC were exposed to pro- (TNFα, IL1β, and IFNγ) and/or anti-inflammatory (IL-10) cytokines and cilia length was quantified. Chronic treatment with all tested inflammatory cytokines led to a significant elongation of cilia in both control human and mouse EC (by ∼1 µm, P < 0.001). This structural response was PKA/PKC dependent. Intriguingly, withdrawal of the inflammatory stimulus did not reduce cilia length. IL-10, on the other hand, blocked and reversed the pro-inflammatory cytokine-induced cilia elongation in healthy ECs, but did not influence basal length. Conversely, primary cilia of ECs from PAH patients were significantly longer under basal cond...Continue Reading

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Citations

Mar 28, 2019·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Akito KakiuchiTakashi Kojima
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BETA
FCS

Software Mentioned

GraphPad Prism
ImageJ
Pythagoras
PyT

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