Nanomaterial- and shape-dependency of TLR2 and TLR4 mediated signaling following pulmonary exposure to carbonaceous nanomaterials in mice
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Nanomaterial- and shape-dependency of TLR2 and TLR4 mediated signaling following pulmonary exposure to carbonaceous nanomaterials in mice. / Danielsen, Pernille Høgh; Bendtsen, Katja Maria; Knudsen, Kristina Bram; Poulsen, Sarah Søs; Stoeger, Tobias; Vogel, Ulla.
I: Particle and Fibre Toxicology, Bind 18, Nr. 1, 40, 2021.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Nanomaterial- and shape-dependency of TLR2 and TLR4 mediated signaling following pulmonary exposure to carbonaceous nanomaterials in mice
AU - Danielsen, Pernille Høgh
AU - Bendtsen, Katja Maria
AU - Knudsen, Kristina Bram
AU - Poulsen, Sarah Søs
AU - Stoeger, Tobias
AU - Vogel, Ulla
N1 - Publisher Copyright: © 2021, The Author(s).
PY - 2021
Y1 - 2021
N2 - Background: Pulmonary exposure to high doses of engineered carbonaceous nanomaterials (NMs) is known to trigger inflammation in the lungs paralleled by an acute phase response. Toll-like receptors (TLRs), particularly TLR2 and TLR4, have recently been discussed as potential NM-sensors, initiating inflammation. Using Tlr2 and Tlr4 knock out (KO) mice, we addressed this hypothesis and compared the pattern of inflammation in lung and acute phase response in lung and liver 24 h after intratracheal instillation of three differently shaped carbonaceous NMs, spherical carbon black (CB), multi-walled carbon nanotubes (CNT), graphene oxide (GO) plates and bacterial lipopolysaccharide (LPS) as positive control. Results: The LPS control confirmed a distinct TLR4-dependency as well as a pronounced contribution of TLR2 by reducing the levels of pulmonary inflammation to 30 and 60% of levels in wild type (WT) mice. At the doses chosen, all NM caused comparable neutrophil influxes into the lungs of WT mice, and reduced levels were only detected for GO-exposed Tlr2 KO mice (35%) and for CNT-exposed Tlr4 KO mice (65%). LPS-induced gene expression was strongly TLR4-dependent. CB-induced gene expression was unaffected by TLR status. Both GO and MWCNT-induced Saa1 expression was TLR4-dependent. GO-induced expression of Cxcl2, Cxcl5, Saa1 and Saa3 were TLR2-dependent. NM-mediated hepatic acute phase response in terms of liver gene expression of Saa1 and Lcn2 was shown to depend on TLR2 for all three NMs. TLR4, in contrast, was only relevant for the acute phase response caused by CNTs, and as expected by LPS. Conclusion: TLR2 and TLR4 signaling was not involved in the acute inflammatory response caused by CB exposure, but contributed considerably to that of GO and CNTs, respectively. The strong involvement of TLR2 in the hepatic acute phase response caused by pulmonary exposure to all three NMs deserves further investigations.
AB - Background: Pulmonary exposure to high doses of engineered carbonaceous nanomaterials (NMs) is known to trigger inflammation in the lungs paralleled by an acute phase response. Toll-like receptors (TLRs), particularly TLR2 and TLR4, have recently been discussed as potential NM-sensors, initiating inflammation. Using Tlr2 and Tlr4 knock out (KO) mice, we addressed this hypothesis and compared the pattern of inflammation in lung and acute phase response in lung and liver 24 h after intratracheal instillation of three differently shaped carbonaceous NMs, spherical carbon black (CB), multi-walled carbon nanotubes (CNT), graphene oxide (GO) plates and bacterial lipopolysaccharide (LPS) as positive control. Results: The LPS control confirmed a distinct TLR4-dependency as well as a pronounced contribution of TLR2 by reducing the levels of pulmonary inflammation to 30 and 60% of levels in wild type (WT) mice. At the doses chosen, all NM caused comparable neutrophil influxes into the lungs of WT mice, and reduced levels were only detected for GO-exposed Tlr2 KO mice (35%) and for CNT-exposed Tlr4 KO mice (65%). LPS-induced gene expression was strongly TLR4-dependent. CB-induced gene expression was unaffected by TLR status. Both GO and MWCNT-induced Saa1 expression was TLR4-dependent. GO-induced expression of Cxcl2, Cxcl5, Saa1 and Saa3 were TLR2-dependent. NM-mediated hepatic acute phase response in terms of liver gene expression of Saa1 and Lcn2 was shown to depend on TLR2 for all three NMs. TLR4, in contrast, was only relevant for the acute phase response caused by CNTs, and as expected by LPS. Conclusion: TLR2 and TLR4 signaling was not involved in the acute inflammatory response caused by CB exposure, but contributed considerably to that of GO and CNTs, respectively. The strong involvement of TLR2 in the hepatic acute phase response caused by pulmonary exposure to all three NMs deserves further investigations.
KW - Acute phase response
KW - Inflammation
KW - Knockout mice
KW - Nanomaterials
KW - Toll-like receptors
U2 - 10.1186/s12989-021-00432-z
DO - 10.1186/s12989-021-00432-z
M3 - Journal article
C2 - 34717665
AN - SCOPUS:85118307777
VL - 18
JO - Particle and Fibre Toxicology
JF - Particle and Fibre Toxicology
SN - 1743-8977
IS - 1
M1 - 40
ER -
ID: 319469377