Self-extracellular RNA acts in synergy with exogenous danger signals to promote inflammation
dc.contributor.author | Noll, Frederik | |
dc.contributor.author | Behnke, Jonas | |
dc.contributor.author | Leiting, Silke | |
dc.contributor.author | Troidl, Kerstin | |
dc.contributor.author | Alves, Gustavo Teixeira | |
dc.contributor.author | Müller-Redetzky, Holger | |
dc.contributor.author | Preissner, Klaus T. | |
dc.contributor.author | Fischer, Silvia | |
dc.date.accessioned | 2022-11-18T09:53:37Z | |
dc.date.available | 2019-05-20T12:40:19Z | |
dc.date.available | 2022-11-18T09:53:37Z | |
dc.date.issued | 2017 | |
dc.description.abstract | Self-extracellular RNA (eRNA), released from stressed or injured cells upon various pathological situations such as ischemia-reperfusion-injury, has been shown to act as an alarmin by inducing procoagulatory and proinflammatory responses. In particular, M1-polarization of macrophages by eRNA resulted in the expression and release of a variety of cytokines, including tumor necrosis factor (TNF)-α or interleukin-6 (IL-6). The present study now investigates in which way self-eRNA may influence the response of macrophages towards various Toll-like receptor (TLR)-agonists. Isolated agonists of TLR2 (Pam2CSK4), TLR3 (PolyIC), TLR4 (LPS), or TLR7 (R848) induced the release of TNF-α in a concentration-dependent manner in murine macrophages, differentiated from bone marrow-derived stem cells by mouse colony stimulating factor. Here, the presence of eRNA shifted the dose-response curve for Pam2CSK4 (Pam) considerably to the left, indicating that eRNA synergistically enhanced the cytokine liberation from macrophages even at very low Pam-levels. The synergistic activation of TLR2 by eRNA/Pam was duplicated by other TLR2-agonists such as FSL-1 or Pam3CSK4. In contrast, for TLR4-agonists such as LPS a synergistic effect of eRNA was much weaker, and was not existent for TLR3-, or TLR7-agonists. The synergistic eRNA/Pam action was dependent on the NFKB-signaling pathway as well as on p38MAP- and MEK1/ERK-kinases and was prevented by predigestion of eRNA with RNase1 or by antibodies against TLR2. Thus, the presence of self-eRNA as alarming molecule sensitizes innate immune responses towards pathogen-associated molecular patterns (PAMPs) in a synergistic way and may thereby contribute to the differentiated outcome of inflammatory responses. | en |
dc.identifier.uri | http://nbn-resolving.de/urn:nbn:de:hebis:26-opus-146144 | |
dc.identifier.uri | https://jlupub.ub.uni-giessen.de//handle/jlupub/9449 | |
dc.identifier.uri | http://dx.doi.org/10.22029/jlupub-8837 | |
dc.language.iso | en | de_DE |
dc.rights | Namensnennung 4.0 International | * |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | * |
dc.subject.ddc | ddc:610 | de_DE |
dc.title | Self-extracellular RNA acts in synergy with exogenous danger signals to promote inflammation | en |
dc.type | article | de_DE |
local.affiliation | FB 08 - Biologie und Chemie | de_DE |
local.opus.fachgebiet | Biologie, Chemie und Geowissenschaften fachübergreifend | de_DE |
local.opus.id | 14614 | |
local.opus.institute | Institute of Biochemistry | de_DE |
local.source.freetext | PLOS ONE 12(12):e0190002 | de_DE |
local.source.uri | https://doi.org/10.1371/journal.pone.0190002 |
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