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Bögel G, Murányi J, Szokol B, et al. Production of NOS2 and inflammatory cytokines is reduced by selected protein kinase inhibitors with partial repolarization of HL-60 derived and human blood macrophages. Heliyon. 2021;8(1):e08670doi: 10.1016/j.heliyon.2021.e08670.
Bögel, G., Murányi, J., Szokol, B., Kukor, Z., Móra, I., Kardon, T., Őrfi, L., & Hrabák, A. (2022). Production of NOS2 and inflammatory cytokines is reduced by selected protein kinase inhibitors with partial repolarization of HL-60 derived and human blood macrophages. Heliyon, 8(1), e08670. https://doi.org/10.1016/j.heliyon.2021.e08670
Bögel, Gábor, et al. "Production of NOS2 and inflammatory cytokines is reduced by selected protein kinase inhibitors with partial repolarization of HL-60 derived and human blood macrophages." Heliyon vol. 8,1 (2022): e08670. doi: https://doi.org/10.1016/j.heliyon.2021.e08670
Bögel G, Murányi J, Szokol B, Kukor Z, Móra I, Kardon T, Őrfi L, Hrabák A. Production of NOS2 and inflammatory cytokines is reduced by selected protein kinase inhibitors with partial repolarization of HL-60 derived and human blood macrophages. Heliyon. 2021 Dec 27;8(1):e08670. doi: 10.1016/j.heliyon.2021.e08670. eCollection 2022 Jan. PMID: 35028455; PMCID: PMC8741463.
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Heliyon. 2021 Dec 27;8(1):e08670. doi: 10.1016/j.heliyon.2021.e08670. eCollection 2022 Jan.

Production of NOS2 and inflammatory cytokines is reduced by selected protein kinase inhibitors with partial repolarization of HL-60 derived and human blood macrophages.

Heliyon

Gábor Bögel, József Murányi, Bálint Szokol, Zoltán Kukor, István Móra, Tamás Kardon, László Őrfi, András Hrabák

Affiliations

  1. Department of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis University, Budapest, H-1094, T?zoltó u. 37-43, Hungary.
  2. MTA-SE Pathobiochemistry Research Group, Budapest, H-1094, T?zoltó u. 37-43, Hungary.
  3. Vichem Chemie Research Ltd., Veszprém, H-8200, Viola u. 2., Hungary.
  4. Department of Pharmaceutical Chemistry, Semmelweis University, Budapest, H-1092, H?gyes E. u. 9., Hungary.

PMID: 35028455 PMCID: PMC8741463 DOI: 10.1016/j.heliyon.2021.e08670

Abstract

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.

© 2021 Published by Elsevier Ltd.

Keywords: Inflammatory cytokines; Kinase inhibitors; M1-M2 polarization signaling; Macrophage; Nitric oxide synthase 2

Conflict of interest statement

The authors declare no conflict of interest.

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