All-Trans Retinoic Acid Promotes M2 Macrophage Polarization in Vitro by Activating the p38MAPK/STAT6 Signaling Pathway

BACKGROUND: M2-type macrophages are inflammation-suppressing cells that are differentiated after induction by cytokines such as IL-4 or IL-13, which play an important regulatory role in inflammation and influence the regression of inflammation-related diseases. All-trans retinoic acid (ATRA) has an important role in suppressing immune-mediated inflammatory responses but the effect and underlying mechanism of ATRA on the polarization of M2 macrophages remains unclear.

METHODS: Macrophages were isolated from peritoneal wash fluid, and IL-4 (20 ng/mL) was used to construct a m2-type macrophage polarization model. The model was incubated with different concentrations of ATRA (15 µg/ml, 30 µg/ml, 45 µg/ml) for 24 h, and pretreated macrophages with p38MAPKα inhibitor SB202190 (20 μM). MTT, Trypan blue staining, Annexin V-PE/7-AAD staining, flow cytometry, real-time PCR and western blotting were used to investigate the effect and mechanism of ATRA on the polarization of M2 macrophages.

RESULTS: Compared with the IL-4 group, the proportion of F4/80+CD206+ M2-type macrophages was significantly higher in the ATRA group (P < 0.01). mRNA and protein expression levels of Arg-1, IL-10 and TGF-β1 were as significantly higher (P < 0.01) in the ATRA group as phosphorylation levels of STAT6 and p38MAPK (P < 0.01). After pretreatment with the addition of the inhibitor SB202190, M2-type macrophages proportion and their associated factors expression were significantly (P < 0.01) reduced, as compared with those in the ATRA group, but they were comparable (P > 0.05) with the IL-4 group.

CONCLUSION: The combination of ATRA and IL-4 activated the p38MAPK/STAT6-signaling pathway to promote polarization of M2 macrophages.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:52

Enthalten in:

Immunological investigations - 52(2023), 3 vom: 22. Apr., Seite 298-318

Sprache:

Englisch

Beteiligte Personen:

Zhu, Ya-Nan [VerfasserIn]
Gu, Xiao-Li [VerfasserIn]
Wang, Lin-Yuan [VerfasserIn]
Guan, Ning [VerfasserIn]
Li, Chen-Guang [VerfasserIn]

Links:

Volltext

Themen:

207137-56-2
5688UTC01R
All-trans retinoic acid
Interleukin-4
Journal Article
M2 macrophage
Macrophage polarization
P38MAPK
Peritoneal macrophages
STAT6
STAT6 Transcription Factor
STAT6 protein, human
Tretinoin

Anmerkungen:

Date Completed 07.04.2023

Date Revised 07.04.2023

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1080/08820139.2023.2173077

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM352413557