Endothelin-1 and its role in the pathogenesis of infectious diseases

Abstract

Endothelins are potent regulators of vascular tone, which also have mitogenic, apoptotic, and immunomodulatory properties [1-3]. Three isoforms of endothelin have been identified to date, with endothelin-1 (ET-1) being the best studied. ET-1 is classically considered a potent vasoconstrictor. However, in addition to the effects of ET-1 on vascular smooth muscle cells, the peptide is increasingly recognized as a pro-inflammatory cytokine [4, 5]. ET-1 causes platelet aggregation and plays a role in the increased expression of leukocyte adhesion molecules, the synthesis of inflammatory mediators contributing to vascular dysfunction. High levels of ET-1 are found in alveolar macrophages, leukocytes [5] and fibroblasts [6]. Clinical and experimental data indicate that ET-1 is involved in the pathogenesis of sepsis [7, 8], viral and bacterial pneumonia [9, 10], Rickettsia conorii infections [11], Chagas disease [12, 13], and severe malaria [14-17]. In this minireview, we will discuss the role of endothelin in the pathogenesis of infectious processes.

Endothelin-1 Treatment Induces an Experimental Cerebral Malaria–Like Syndrome in C57BL/6 Mice Infected with Plasmodium berghei NK65

“…14,20,21,47 In the current study, we investigated the ability of ET-1 to induce an ECM-like phenotype in a mouse model that generally does not develop ECM. We examined behavioral, histopathologic, and cerebrovascular parameters in B6 mice infected with PbN and treated with exogenous ET-1 in comparison to PbN-infected B6 mice given NS or to PbAinfected mice.…”

Mexico City normal weight children exposed to high concentrations of ambient PM2.5 show high blood leptin and endothelin-1, vitamin D deficiency, and food reward hormone dysregulation versus low pollution controls. Relevance for obesity and Alzheimer disease

“…Mexico City children showed dysregulation of feeding regulatory hormones including glucagonlike peptide-1, ghrelin, and glucagon, also involved in the modulation of reward processes, motivated behaviors and cognitive performances (Monteleone and Maj, 2013). Residency in a polluted environment results in altered appetite-regulating peptides and increases in endothelin-1 -a powerful vasoconstrictor and proinflammatory mediator (Teder and Noble, 2000;Freeman et al, 2014;Bickford et al, 2014). To worsen the scenario, these children also have marked vitamin D deficiency.…”

Rendomab B4, a monoclonal antibody that discriminates the human endothelin B receptor of melanoma cells and inhibits their migration

“…Binding properties of anti-human ETB specific monoclonal antibodies. To evaluate maximal binding (A) and apparent affinities (B, C), CHO and UACC-257 cells expressing hETB were incubated for 24 h at 4 C with increasing concentrations of ETB directed antibodies. Binding of anti-ETB antibodies were revealed using R-PElabeled anti-mouse antibody and quantified by flow cytometry.…”

“…After 48 h, cells were washed in PBS and fixed for 15 min in 4% paraformaldehyde (PFA) at room temperature. Cells were then incubated for 10 min in 50 mM NH 4 Cl and washed once with PBS. Cells were then incubated at room temperature for 1 hour in the presence of 100 nM of rendomab-B4 in PBS-1% BSA.…”

“…ET-1 plays a crucial role in the regulation of physiological smooth muscle motility, [1][2][3] but ET-1 is also implicated in a large variety of pathologies, including hypertension, heart failure, kidney disorders and infectious diseases. [4][5][6] In addition, the ET axis is overexpressed in cancer of different organs contributing to tumor growth by acting on cell proliferation, survival, migration, differentiation, angiogenesis and inflammatory cell recruitment. 7,8 ETA are upregulated in prostate, 9 ovary 10 and breast cancers while ETB is overexpressed in melanoma.…”