PMID- 36754230
OWN - NLM
STAT- MEDLINE
DCOM- 20230223
LR  - 20240402
IS  - 1879-2618 (Electronic)
IS  - 1388-1981 (Print)
IS  - 1388-1981 (Linking)
VI  - 1868
IP  - 4
DP  - 2023 Apr
TI  - Functional characterization of interleukin 4 and retinoic acid signaling 
      crosstalk during alternative macrophage activation.
PG  - 159291
LID - S1388-1981(23)00015-X [pii]
LID - 10.1016/j.bbalip.2023.159291 [doi]
AB  - Retinoic acid possesses potent immunomodulatory properties in various cell types, 
      including macrophages. In this study, we first investigated the effects at the 
      transcriptional and functional levels of exogenous retinoic acid in murine bone 
      marrow-derived macrophages (BMDMs) in the presence or absence of interleukin 4 
      (IL4), a cytokine with potent anti-inflammatory properties. We examined the 
      effect of IL4 on vitamin A homeostasis in macrophages by quantifying retinoid 
      synthesis and secretion. Our RNAseq data show that exogenous retinoic acid 
      synergizes with IL4 to regulate anti-inflammatory pathways such as oxidative 
      phosphorylation and phagocytosis. Efferocytosis and lysosomal degradation assays 
      validated gene expression changes at the functional level. IL4 treatment altered 
      the expression of several genes involved in vitamin A transport and conversion to 
      retinoic acid. Radiolabeling experiments and mass spectrometry assays revealed 
      that IL4 stimulates retinoic acid production and secretion in a signal transducer 
      and activator of transcription 6 (STAT6)-dependent manner. In summary, our 
      studies highlight the key role of exogenous and endogenous retinoic acid in 
      shaping the anti-inflammatory response of macrophages.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Pinos, Ivan
AU  - Pinos I
AD  - Division of Nutritional Sciences, University of Illinois Urbana Champaign, 
      Urbana, IL, United States.
FAU - Yu, Jianshi
AU  - Yu J
AD  - Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 
      Baltimore, MD, United States.
FAU - Pilli, Nageswara
AU  - Pilli N
AD  - Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 
      Baltimore, MD, United States.
FAU - Kane, Maureen A
AU  - Kane MA
AD  - Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 
      Baltimore, MD, United States.
FAU - Amengual, Jaume
AU  - Amengual J
AD  - Division of Nutritional Sciences, University of Illinois Urbana Champaign, 
      Urbana, IL, United States; Department of Food Science and Human Nutrition, 
      University of Illinois Urbana Champaign, Urbana, IL, United States. Electronic 
      address: jaume6@illinois.edu.
LA  - eng
GR  - R01 HL147252/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20230206
PL  - Netherlands
TA  - Biochim Biophys Acta Mol Cell Biol Lipids
JT  - Biochimica et biophysica acta. Molecular and cell biology of lipids
JID - 101731727
RN  - 5688UTC01R (Tretinoin)
RN  - 207137-56-2 (Interleukin-4)
RN  - 11103-57-4 (Vitamin A)
RN  - 0 (Anti-Inflammatory Agents)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Tretinoin/pharmacology
MH  - *Interleukin-4/metabolism
MH  - Vitamin A
MH  - Macrophage Activation
MH  - Anti-Inflammatory Agents
PMC - PMC9974901
MID - NIHMS1873465
OTO - NOTNLM
OT  - Immunometabolism
OT  - Macrophage
OT  - Retinoids
OT  - Vitamin A
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/02/09 06:00
MHDA- 2023/02/25 06:00
PMCR- 2024/04/01
CRDT- 2023/02/08 19:25
PHST- 2022/11/19 00:00 [received]
PHST- 2023/01/25 00:00 [revised]
PHST- 2023/01/28 00:00 [accepted]
PHST- 2023/02/09 06:00 [pubmed]
PHST- 2023/02/25 06:00 [medline]
PHST- 2023/02/08 19:25 [entrez]
PHST- 2024/04/01 00:00 [pmc-release]
AID - S1388-1981(23)00015-X [pii]
AID - 10.1016/j.bbalip.2023.159291 [doi]
PST - ppublish
SO  - Biochim Biophys Acta Mol Cell Biol Lipids. 2023 Apr;1868(4):159291. doi: 
      10.1016/j.bbalip.2023.159291. Epub 2023 Feb 6.