PMID- 31391499
OWN - NLM
STAT- MEDLINE
DCOM- 20201106
LR  - 20210110
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 9
IP  - 1
DP  - 2019 Aug 7
TI  - High Glucose Environments Interfere with Bone Marrow-Derived Macrophage 
      Inflammatory Mediator Release, the TLR4 Pathway and Glucose Metabolism.
PG  - 11447
LID - 10.1038/s41598-019-47836-8 [doi]
LID - 11447
AB  - Macrophages may be a crucial aspect of diabetic complications associated with the 
      inflammatory response. In this study, we examined how hyperglycaemia, a common 
      aspect of diabetes, modulates bone marrow-derived macrophages (BMDMs) under an 
      inflammatory stimulus. To perform this study, BMDMs from non-diabetic and 
      diabetic (60 mg/kg alloxan, i.v.) male C57BL/6 mice (CEUA/FCF/USP-488) were 
      cultured under normal (5.5 mM) and high glucose (HG, 25 or 40 mM) conditions and 
      stimulated or not stimulated with lipopolysaccharide (LPS, 100 ng/mL). Compared 
      to the BMDMs from the normoglycaemic mice, the LPS-stimulated BMDMs from the 
      diabetic mice presented reduced TLR4 expression on the cell surface, lower 
      phagocytic capacity, and reduced secretion of NO and lactate but greater oxygen 
      consumption and greater phosphorylation of p46 SAPK/JNK, p42 ERK MAPK, pAKT and 
      pPKC-delta. When the BMDMs from the non-diabetic mice were cultured under 
      high-glucose conditions and stimulated with LPS, TLR4 expression was reduced on 
      the cell surface and NO and H(2)O(2) levels were reduced. In contrast, the 
      diabetic BMDMs cultured under high glucose conditions presented increased levels 
      of lactate and reduced phosphorylation of AKT, PKC-delta and p46 SAPK/JNK but 
      enhanced phosphorylation of the p46 subunit of SAPK/JNK after LPS stimulation. 
      High glucose levels appear to modify macrophage behaviour, affecting different 
      aspects of diabetic and healthy BMDMs under the same LPS stimulus. Thus, 
      hyperglycaemia leaves a glucose legacy, altering the basal steady state of 
      macrophages.
FAU - Ayala, Thais Soprani
AU  - Ayala TS
AD  - Laboratory of Immunoendocrinology, Department of Clinical and Toxicological 
      Analyses, School of Pharmaceutical Sciences of University Sao Paulo (FCF/USP), 
      Sao Paulo, Brazil.
FAU - Tessaro, Fernando Henrique Galvao
AU  - Tessaro FHG
AUID- ORCID: 0000-0002-0389-5976
AD  - Laboratory of Immunoendocrinology, Department of Clinical and Toxicological 
      Analyses, School of Pharmaceutical Sciences of University Sao Paulo (FCF/USP), 
      Sao Paulo, Brazil.
FAU - Jannuzzi, Grasielle Pereira
AU  - Jannuzzi GP
AD  - Laboratory of Cellular Immunology and Biochemistry of Fungus and Protozoa, 
      Department of Pharmaceutical Sciences Analysis, Federal University of Sao Paulo, 
      Sao Paulo, Brazil.
FAU - Bella, Leonardo Mendes
AU  - Bella LM
AD  - Laboratory of Immunoendocrinology, Department of Clinical and Toxicological 
      Analyses, School of Pharmaceutical Sciences of University Sao Paulo (FCF/USP), 
      Sao Paulo, Brazil.
FAU - Ferreira, Karen Spadari
AU  - Ferreira KS
AD  - Laboratory of Cellular Immunology and Biochemistry of Fungus and Protozoa, 
      Department of Pharmaceutical Sciences Analysis, Federal University of Sao Paulo, 
      Sao Paulo, Brazil.
FAU - Martins, Joilson O
AU  - Martins JO
AUID- ORCID: 0000-0003-2630-7038
AD  - Laboratory of Immunoendocrinology, Department of Clinical and Toxicological 
      Analyses, School of Pharmaceutical Sciences of University Sao Paulo (FCF/USP), 
      Sao Paulo, Brazil. martinsj@usp.br.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190807
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Blood Glucose)
RN  - 0 (Culture Media)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - 6SW5YHA5NG (Alloxan)
SB  - IM
MH  - Alloxan/toxicity
MH  - Animals
MH  - Blood Glucose/immunology/*metabolism
MH  - Cells, Cultured
MH  - Culture Media/metabolism
MH  - Diabetes Mellitus, Experimental/blood/chemically induced/*immunology
MH  - Humans
MH  - Inflammation Mediators/*metabolism
MH  - Lipopolysaccharides/immunology
MH  - Macrophages/*immunology/metabolism
MH  - Male
MH  - Mice
MH  - Primary Cell Culture
MH  - Signal Transduction/immunology
MH  - Toll-Like Receptor 4/immunology/*metabolism
PMC - PMC6686006
COIS- The authors declare no competing interests.
EDAT- 2019/08/09 06:00
MHDA- 2020/11/11 06:00
PMCR- 2019/08/07
CRDT- 2019/08/09 06:00
PHST- 2019/01/28 00:00 [received]
PHST- 2019/07/25 00:00 [accepted]
PHST- 2019/08/09 06:00 [entrez]
PHST- 2019/08/09 06:00 [pubmed]
PHST- 2020/11/11 06:00 [medline]
PHST- 2019/08/07 00:00 [pmc-release]
AID - 10.1038/s41598-019-47836-8 [pii]
AID - 47836 [pii]
AID - 10.1038/s41598-019-47836-8 [doi]
PST - epublish
SO  - Sci Rep. 2019 Aug 7;9(1):11447. doi: 10.1038/s41598-019-47836-8.