PMID- 37546857
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230807
DP  - 2023 Jul 27
TI  - Transcriptomic Effects of Low-Dose Inorganic Arsenic Exposure on Murine Bone 
      Marrow-Derived Macrophages.
LID - 2023.07.26.550543 [pii]
LID - 10.1101/2023.07.26.550543 [doi]
AB  - Both tissue-resident macrophages and monocytes recruited from the bone marrow 
      that transform into tissue-resident cells play critical roles in mediating 
      homeostasis as well as in the pathology of inflammatory diseases. Inorganic 
      arsenic (iAs) is the most common drinking water contaminant worldwide and 
      represents a major public health concern. Several diseases that macrophages have 
      implicated involvement in are caused by iAs exposure, including cardiovascular 
      disease, cancer, and increased risk of infectious disease. Therefore, 
      understanding the effects of iAs exposure on macrophages can help us better grasp 
      the full range of arsenic immunotoxicity and better design therapeutic targets 
      for iAs-induced diseases particularly in exposed populations. In this study, we 
      analyzed the transcriptome of low dose iAs-exposed male and female murine bone 
      marrow-derived macrophages (BMDMs) with either M0, M1, or M2 stimulation. We 
      identified differentially expressed genes by iAs in a sex- and 
      stimulation-dependent manner and used bioinformatics tools to predict 
      protein-protein interactions, transcriptional regulatory networks, and associated 
      biological processes. Overall, our data suggest that M1-stimulated, especially 
      female-derived, BMDMs are most susceptible to iAs exposure. Most notably, we 
      observed significant downregulation of major proinflammatory transcription 
      factors, like IRF8, and its downstream targets, as well as genes encoding 
      proteins involved in pattern recognition and antigen presentation, such as TLR7, 
      TLR8, and H2-D1, potentially providing causal insight regarding arsenic's role in 
      perturbing immune responses to infectious diseases. We also observed significant 
      downregulation of genes involved in processes crucial to coordinating a 
      proinflammatory response including leukocyte migration, differentiation, and 
      cytokine and chemokine production and response. Finally, we discovered that 24 
      X-linked genes were dysregulated in iAs-exposed female stimulation groups 
      compared to only 3 across the iAs-exposed male stimulation groups. These findings 
      elucidate the potential mechanisms underlying the sex-differential iAs-associated 
      immune-related disease risk.
FAU - Illingworth, Emily J
AU  - Illingworth EJ
AUID- ORCID: 0000-0003-1224-2990
FAU - Maertens, Alexandra
AU  - Maertens A
AUID- ORCID: 0000-0002-2077-2011
FAU - Sille, Fenna C M
AU  - Sille FCM
AUID- ORCID: 0000-0002-9016-9621
LA  - eng
PT  - Preprint
DEP - 20230727
PL  - United States
TA  - bioRxiv
JT  - bioRxiv : the preprint server for biology
JID - 101680187
PMC - PMC10402011
EDAT- 2023/08/07 06:41
MHDA- 2023/08/07 06:42
PMCR- 2023/08/04
CRDT- 2023/08/07 04:43
PHST- 2023/08/07 06:42 [medline]
PHST- 2023/08/07 06:41 [pubmed]
PHST- 2023/08/07 04:43 [entrez]
PHST- 2023/08/04 00:00 [pmc-release]
AID - 2023.07.26.550543 [pii]
AID - 10.1101/2023.07.26.550543 [doi]
PST - epublish
SO  - bioRxiv [Preprint]. 2023 Jul 27:2023.07.26.550543. doi: 
      10.1101/2023.07.26.550543.