Brain capillary pericytes contribute to the immune defense in response to cytokines or LPS in vitro

Pieper, Christian; Marek, Jasmin J.; Unterberg, Marlies; Schwerdtle, Tanja; Galla, Hans‐Joachim

doi:10.1016/j.brainres.2014.01.004

Cited by 104 publications

(93 citation statements)

References 25 publications

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“…Pericytes also present inflammatory cues and release inflammatory mediators including IL-1ș, IL-6, TNFȘ, ROS, NO and matrix metalloproteinases when activated with immune stimuli (Jansson et al, 2014;Kovac et al, 2011;Proebstl et al, 2012;Stark et al, 2013;Wang et al, 2012). They can even assume a macrophage phenotype and migrate to perivascular space, becoming indistinguishable from resident macrophages and activated microglia (Balabanov et al, 1996;Hurtado-Alvarado et al, 2014;Ozen et al, 2012;Pieper et al, 2014;Thomas, 1999). Pericytes initially respond to an inflammatory stimulus by increased expression of pro-inflammatory cytokines (Hurtado-Alvarado et al, 2014), which open tight junctions and facilitate entry of inflammatory cells into the vessel wall (Alvarez and Teale, 2007).…”

Section: 3-inflammation and Pericytesmentioning

confidence: 97%

Cerebral microvascular pericytes and neurogliovascular signaling in health and disease

2015

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Section: 3-inflammation and Pericytesmentioning

confidence: 97%

Cerebral microvascular pericytes and neurogliovascular signaling in health and disease

2015

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“…Pericytes can act as perivascular tissue macrophages to clear tissue debris and foreign proteins injected systemically and/or locally in the CNS 2,9,10,26,27 and participate in clearance of Alzheimer's amyloid-β (Aβ) toxin, as shown in AD mice 26 .…”

Section: Pericytes: Characterization Function and Dysfunctionmentioning

confidence: 99%

Pericytes of the neurovascular unit: key functions and signaling pathways

Ayyadurai²,

2016

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Pericytes are vascular mural cells embedded in the basement membrane of blood microvessels. They extend their processes along capillaries, pre-capillary arterioles, and post-capillary venules. The central nervous system (CNS) pericytes are uniquely positioned within the neurovascular unit between endothelial cells, astrocytes, and neurons. They integrate, coordinate, and process signals from their neighboring cells to generate diverse functional responses that are critical for CNS functions in health and disease including regulation of the blood-brain barrier permeability, angiogenesis, clearance of toxic metabolites, capillary hemodynamic responses, neuroinflammation, and stem cell activity. Here, we examine the key signaling pathways between pericytes and their neighboring endothelial cells, astrocytes, and neurons that control neurovascular functions. We also review the role of pericytes in different CNS disorders including rare monogenic diseases and complex neurological disorders such as Alzheimer's disease and brain tumors. Finally, we discuss directions for future studies.

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“…In contrast to the numerous studies assessing the crosstalk among brain endothelial cells, astrocytes and microglia during inflammation, little is known about the role played by the brain microvascular pericyte. In fact, the response of brain pericytes to pro‐inflammatory stimuli has only been addressed in the last few years 2, 3, 4. In a pioneering work, Kovac et al .…”

Section: Introductionmentioning

confidence: 99%

Role of nucleotide‐binding oligomerization domain 1 (NOD1) in pericyte‐mediated vascular inflammation

Navarro

Delgado-Wicke

Nuñez-Prado

et al. 2016

J Cellular Molecular Medi

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We have recently described the response of human brain pericytes to lipopolysaccharide (LPS) through toll‐like receptor 4 (TLR4). However, Gram‐negative pathogen‐associated molecular patterns include not only LPS but also peptidoglycan (PGN). Given that the presence of co‐purified PGN in the LPS preparation previously used could not be ruled out, we decided to analyse the expression of the intracellular PGN receptors NOD1 and NOD2 in HBP and compare the responses to their cognate agonists and ultrapure LPS.Our findings show for the first time that NOD1 is expressed in pericytes, whereas NOD2 expression is barely detectable. The NOD1 agonist C12‐iE‐DAP induced IL6 and IL8 gene expression by pericytes as well as release of cytokines into culture supernatant. Moreover, we demonstrated the synergistic effects of NOD1 and TLR4 agonists on the induction of IL8. Using NOD1 silencing in HBP, we showed a requirement for C12‐iE‐DAP‐dependent signalling. Finally, we could discriminate NOD1 and TLR4 pathways in pericytes by pharmacological targeting of RIPK2, a kinase involved in NOD1 but not in TLR4 signalling cascade. p38 MAPK and NF‐κB appear to be downstream mediators in the NOD1 pathway.In summary, these results indicate that pericytes can sense Gram‐negative bacterial products by both NOD1 and TLR4 receptors, acting through distinct pathways. This provides new insight about how brain pericytes participate in the inflammatory response and may have implications for disease management.

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Brain capillary pericytes contribute to the immune defense in response to cytokines or LPS in vitro

Cited by 104 publications

References 25 publications

Cerebral microvascular pericytes and neurogliovascular signaling in health and disease

Cerebral microvascular pericytes and neurogliovascular signaling in health and disease

Pericytes of the neurovascular unit: key functions and signaling pathways

Role of nucleotide‐binding oligomerization domain 1 (NOD1) in pericyte‐mediated vascular inflammation

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