PMID- 32292895
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240403
IS  - 2576-3113 (Electronic)
IS  - 2576-3105 (Print)
IS  - 2576-3105 (Linking)
VI  - 2
IP  - 1
DP  - 2020 Mar 1
TI  - Interferon-Gamma Stimulated Murine Macrophages In Vitro: Impact of Ionic 
      Composition and Osmolarity and Therapeutic Implications.
PG  - 48-58
LID - 10.1089/bioe.2019.0032 [doi]
AB  - Background: Injections of osmolytes are promising immunomodulatory treatments for 
      medical benefit, although the rationale and underlying mechanisms are often 
      lacking. The goals of the present study were twofold: (1) to clarify the 
      anti-inflammatory role of the potassium ion and (2) to begin to decouple the 
      effects that ionic strength, ionic species, and osmolarity have on macrophage 
      biology. Materials and Methods: RAW 264.7 murine macrophages were encapsulated in 
      three-dimensional, poly(ethylene glycol) diacrylate hydrogels and activated with 
      interferon-gamma to yield M(IFN). Gene and protein profiles were made of M(IFN) 
      exposed to different hyperosmolar treatments (80 mM potassium gluconate, 80 mM 
      sodium gluconate, and 160 mM sucrose). Results: Relative to M(IFN), all 
      hyperosmolar treatments suppressed expression of pro-inflammatory markers (nitric 
      oxide synthase-2 [NOS-2], tumor necrosis factor-alpha, monocyte chemoattractant 
      protein-1 [MCP-1]) and increased messenger RNA (mRNA) expression of the 
      pleiotropic and angiogenic markers interleukin-6 (IL-6) and vascular endothelial 
      growth factor-A (VEGF), respectively. Ionic osmolytes also demonstrated a greater 
      level of change compared to the nonionic treatments, with mRNA levels of IL-6 the 
      most significantly affected. M(IFN) exposed to K(+) exhibited the lowest levels 
      of NOS-2 and MCP-1, and this ion limited IL-6 release induced by osmolarity. 
      Conclusion: Cumulatively, these data suggest that osmolyte composition, ionic 
      strength, and osmolarity are all parameters that can influence therapeutic 
      outcomes. Future work is necessary to further decouple and mechanistically 
      understand the influence that these biophysical parameters have on cell biology, 
      including their impact on other macrophage functions, intracellular osmolyte 
      composition, and cellular and organellular membrane potentials.
CI  - Copyright 2020, Mary Ann Liebert, Inc., publishers.
FAU - Erndt-Marino, Joshua
AU  - Erndt-Marino J
AD  - Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, New 
      York.
AD  - Department of Biomedical Engineering, Tufts University, Medford, Massachusetts.
AD  - Department of Biology, Allen Discovery Center at Tufts University, Tufts 
      University, Medford, Massachusetts.
FAU - Yeisley, Daniel J
AU  - Yeisley DJ
AD  - Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, New 
      York.
FAU - Chen, Hongyu
AU  - Chen H
AD  - Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, New 
      York.
FAU - Levin, Michael
AU  - Levin M
AD  - Department of Biology, Allen Discovery Center at Tufts University, Tufts 
      University, Medford, Massachusetts.
FAU - Kaplan, David L
AU  - Kaplan DL
AD  - Department of Biomedical Engineering, Tufts University, Medford, Massachusetts.
AD  - Department of Biology, Allen Discovery Center at Tufts University, Tufts 
      University, Medford, Massachusetts.
FAU - Hahn, Mariah S
AU  - Hahn MS
AD  - Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, New 
      York.
LA  - eng
GR  - F32 MH118678/MH/NIMH NIH HHS/United States
PT  - Journal Article
DEP - 20200318
PL  - United States
TA  - Bioelectricity
JT  - Bioelectricity
JID - 101747121
PMC - PMC7107958
OTO - NOTNLM
OT  - 3D culture
OT  - hyperosmolarity
OT  - inflammation
OT  - ions
OT  - macrophages
OT  - membrane voltage potential
COIS- J.E.-M. and M.S.H. have a patent related to this work (US Patent App. 16/285,348, 
      2019).
EDAT- 2020/04/16 06:00
MHDA- 2020/04/16 06:01
PMCR- 2021/03/01
CRDT- 2020/04/16 06:00
PHST- 2020/04/16 06:00 [entrez]
PHST- 2020/04/16 06:00 [pubmed]
PHST- 2020/04/16 06:01 [medline]
PHST- 2021/03/01 00:00 [pmc-release]
AID - 10.1089/bioe.2019.0032 [pii]
AID - 10.1089/bioe.2019.0032 [doi]
PST - ppublish
SO  - Bioelectricity. 2020 Mar 1;2(1):48-58. doi: 10.1089/bioe.2019.0032. Epub 2020 Mar 
      18.