PMID- 30099064
OWN - NLM
STAT- MEDLINE
DCOM- 20180904
LR  - 20180904
IS  - 1879-3169 (Electronic)
IS  - 0378-4274 (Linking)
VI  - 296
DP  - 2018 Oct 15
TI  - Aryl hydrocarbon receptor activation by benzo(a)pyrene inhibits proliferation of 
      myeloid precursor cells and alters the differentiation state as well as the 
      functional phenotype of murine bone marrow-derived macrophages.
PG  - 106-113
LID - S0378-4274(18)31537-6 [pii]
LID - 10.1016/j.toxlet.2018.07.050 [doi]
AB  - Intensive research during the past decade has highlighted the impact of the 
      regulatory function of the aryl hydrocarbon receptor (AhR) in immunity. In this 
      study, we focused on the influence of AhR activation on the differentiation of 
      murine bone marrow-derived myeloid precursor cells into mature macrophages. Our 
      results show that the activation of AhR by subtoxic doses of the AhR ligand 
      benzo(a)pyrene (BaP) impaired the proliferation of bone marrow cells (BMCs) 
      whereas the proportion of resulting adherent cells was not affected. Flow 
      cytometric analysis revealed that the number of mature bone marrow-derived 
      macrophages (BMMs) was significantly decreased by AhR activation. However, 
      expression of the murine macrophage marker F4/80, the major histocompatibility 
      complex class II (MHC-II) and the Fcgamma receptor I (FcgammaRI/CD64) were upregulated on 
      BaP-exposed BMMs in an AhR-dependent manner. Analysis of cytokine secretion after 
      BMM activation with heat-killed (hk) salmonellae showed that BaP exposure 
      resulted in suppressed secretion of interleukin (IL)-1beta, IL-6 and the chemokine 
      CXC motif ligand 1 (CXCL1). In contrast, the release of tumor necrosis factor 
      (TNF)-alpha and IL-10 was increased following BaP exposure. In addition, the 
      production of antimicrobial nitric oxide (NO) was increased AhR-dependently. 
      Bacterial stimulation of BaP exposed BMMs also induced the expression of MHC-II 
      and CD64, while the expression of F4/80 was dramatically decreased. In summary, 
      this study demonstrates for the first time that sustained exposure over 6 days of 
      bone marrow-derived myeloid precursors to subtoxic doses of BaP critically 
      interferes with differentiation and activation of BMMs. We could convincingly 
      show that AhR-induced gene regulation is crucial for homeostasis of pro- and 
      anti-inflammatory cytokines during macrophage activation.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Riemschneider, Sina
AU  - Riemschneider S
AD  - Department of Therapy Validation, Fraunhofer Institute for Cell Therapy and 
      Immunology, 04103, Leipzig, Germany. Electronic address: 
      sina.riemschneider@izi.fraunhofer.de.
FAU - Kohlschmidt, Janine
AU  - Kohlschmidt J
AD  - Department of Therapy Validation, Fraunhofer Institute for Cell Therapy and 
      Immunology, 04103, Leipzig, Germany. Electronic address: 
      janine.kohlschmidt@izi.fraunhofer.de.
FAU - Fueldner, Christiane
AU  - Fueldner C
AD  - Department of Therapy Validation, Fraunhofer Institute for Cell Therapy and 
      Immunology, 04103, Leipzig, Germany. Electronic address: 
      christiane.fueldner@zv.uni-leipzig.de.
FAU - Esser, Charlotte
AU  - Esser C
AD  - Leibniz Research Institute for Environmental Medicine, 40225, Dusseldorf, 
      Germany. Electronic address: charlotte.esser@uni-duesseldorf.de.
FAU - Hauschildt, Sunna
AU  - Hauschildt S
AD  - Department of Immunobiology, Faculty of Life Sciences, University of Leipzig, 
      04103, Leipzig, Germany. Electronic address: shaus@rz.uni-leipzig.de.
FAU - Lehmann, Jorg
AU  - Lehmann J
AD  - Department of Therapy Validation, Fraunhofer Institute for Cell Therapy and 
      Immunology, 04103, Leipzig, Germany. Electronic address: 
      joerg.lehmann@izi.fraunhofer.de.
LA  - eng
PT  - Journal Article
DEP - 20180809
PL  - Netherlands
TA  - Toxicol Lett
JT  - Toxicology letters
JID - 7709027
RN  - 0 (Antigens, Differentiation)
RN  - 0 (Biomarkers)
RN  - 0 (Cytokines)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 0 (monocyte-macrophage differentiation antigen)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 3417WMA06D (Benzo(a)pyrene)
SB  - IM
MH  - Animals
MH  - Antigens, Differentiation/metabolism
MH  - Benzo(a)pyrene/*pharmacology
MH  - Biomarkers/metabolism
MH  - Bone Marrow Cells/*drug effects
MH  - Cell Differentiation/*drug effects
MH  - Cell Proliferation/*drug effects
MH  - Cytokines/metabolism
MH  - Genes, MHC Class II/drug effects
MH  - Macrophages/*drug effects
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myeloid Progenitor Cells/*drug effects
MH  - Nitric Oxide/metabolism
MH  - Phenotype
MH  - Receptors, Aryl Hydrocarbon/*agonists
OTO - NOTNLM
OT  - Aryl hydrocarbon receptor (AhR)
OT  - Benzo(a)pyrene (BaP)
OT  - Differentiation
OT  - Macrophage
EDAT- 2018/08/14 06:00
MHDA- 2018/09/05 06:00
CRDT- 2018/08/13 06:00
PHST- 2018/03/08 00:00 [received]
PHST- 2018/07/13 00:00 [revised]
PHST- 2018/07/26 00:00 [accepted]
PHST- 2018/08/14 06:00 [pubmed]
PHST- 2018/09/05 06:00 [medline]
PHST- 2018/08/13 06:00 [entrez]
AID - S0378-4274(18)31537-6 [pii]
AID - 10.1016/j.toxlet.2018.07.050 [doi]
PST - ppublish
SO  - Toxicol Lett. 2018 Oct 15;296:106-113. doi: 10.1016/j.toxlet.2018.07.050. Epub 
      2018 Aug 9.