Production of NOS2 and inflammatory cytokines is reduced by selected protein kinase inhibitors with partial repolarization of HL-60 derived and human blood macrophages.
Inflammatory cytokines
Kinase inhibitors
M1-M2 polarization signaling
Macrophage
Nitric oxide synthase 2
Journal
Heliyon
ISSN: 2405-8440
Titre abrégé: Heliyon
Pays: England
ID NLM: 101672560
Informations de publication
Date de publication:
Jan 2022
Jan 2022
Historique:
received:
12
07
2021
revised:
10
11
2021
accepted:
21
12
2021
entrez:
14
1
2022
pubmed:
15
1
2022
medline:
15
1
2022
Statut:
epublish
Résumé
JAK/STAT pathway plays a well-known role in macrophage polarization, but other signaling routes may also be involved. The aim of this study was to identify new signaling pathways and repolarize macrophages by selected protein kinase inhibitors. HL-60 derived macrophages were chosen as model cells and human blood macrophages were used for comparison. M1 and M2 polarization of HL60 derived and human blood macrophages was promoted by LPS + IFNγ (LIF) and IL-4 treatments, respectively. In HL-60 derived macrophages, M1 polarization was mediated by Erk1/2 and p38 phosphorylation, while HSP27 phosphorylation was involved in M2 polarization. The inhibition of both MAPK and JAK/STAT pathways reduced the expression of NOS2, IP-10 and TNFα, IL-8 production was decreased by the inhibition of AMPK and PKD, the upstream kinase of HSP27. HSP27 phosphorylation was inhibited by NB 142, a PKD inhibitor. The expression of CD80 (M1 marker) was reduced by MAPK and JAK/STAT inhibitors, without increasing CD206 (M2 marker). On the other hand, CD206 was reduced by PKD and AMPK inhibitors, without increasing CD80 marker. Phagocytic capacity of HL-60 derived macrophages was higher in M1 macrophages and decreased by trametinib and a p38 inhibitor, while in human blood macrophages, where AT 9283, a JAK/STAT inhibitor also caused a significant decrease in M1 polarized macrophages, no difference was observed between M1 and M2 macrophages. Our results suggest that the repolarization of macrophages cannot be achieved by inhibiting their signaling pathways; nevertheless, the expression of certain polarization markers was decreased, therefore a "depolarization" could be observed both in M1 and M2 polarized cells. Selected protein kinase inhibitors of M1 polarization, decreasing NOS 2 and inflammatory cytokines may be potential candidates for therapeutical trials against inflammatory diseases.
Identifiants
pubmed: 35028455
doi: 10.1016/j.heliyon.2021.e08670
pii: S2405-8440(21)02773-0
pmc: PMC8741463
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e08670Informations de copyright
© 2021 Published by Elsevier Ltd.
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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