Differential Cytokine-Induced Responses of Polarized Microglia

The role of select pro- and anti-inflammatory mediators in driving microglial cell polarization into classically (M1), or alternatively, (M2) activated states, as well as the subsequent differential responses of these induced phenotypes, was examined. Expression of PD-L1, MHC-II, MHC-I, arginase 1 (...

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Autores principales:	Priyanka Chauhan, Wen S. Sheng, Shuxian Hu, Sujata Prasad, James R. Lokensgard
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	microglia cytokines microglial polarization programmed death-ligand 1 (PD-L1) Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/917a425cb0ef40cd92bcca0d27ca452f
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spelling	oai:doaj.org-article:917a425cb0ef40cd92bcca0d27ca452f2021-11-25T16:58:14ZDifferential Cytokine-Induced Responses of Polarized Microglia10.3390/brainsci111114822076-3425https://doaj.org/article/917a425cb0ef40cd92bcca0d27ca452f2021-11-01T00:00:00Zhttps://www.mdpi.com/2076-3425/11/11/1482https://doaj.org/toc/2076-3425The role of select pro- and anti-inflammatory mediators in driving microglial cell polarization into classically (M1), or alternatively, (M2) activated states, as well as the subsequent differential responses of these induced phenotypes, was examined. Expression of PD-L1, MHC-II, MHC-I, arginase 1 (Arg-1), and inducible nitric oxide synthase (iNOS) was assessed using multi-color flow cytometry. We observed that both pro- and anti-inflammatory mediators induced PD-L1 expression on non-polarized microglia. Moreover, IFN-γ stimulated significant MHC class I and II expression on these cells. Interestingly, we observed that only IL-4 treatment induced Arg-1 expression, indicating M2 polarization. These M2 cells were refractory to subsequent depolarization and maintained their alternatively activated state. Furthermore, PD-L1 expression was significantly induced on these M2-polarized microglia after treatment with pro-inflammatory mediators, but not anti-inflammatory cytokines. In addition, we observed that only LPS induced iNOS expression in microglial cells, indicating M1 polarization. Furthermore, IFN-γ significantly increased the percentage of M1-polarized microglia expressing iNOS. Surprisingly, when these M1-polarized microglia were treated with either IL-6 or other anti-inflammatory cytokines, they returned to their non-polarized state, as demonstrated by significantly reduced expression of iNOS. Taken together, these results demonstrate differential responses of microglial cells to mediators present in dissimilar microenvironments.Priyanka ChauhanWen S. ShengShuxian HuSujata PrasadJames R. LokensgardMDPI AGarticlemicrogliacytokinesmicroglial polarizationprogrammed death-ligand 1 (PD-L1)Neurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENBrain Sciences, Vol 11, Iss 1482, p 1482 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	microglia cytokines microglial polarization programmed death-ligand 1 (PD-L1) Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	microglia cytokines microglial polarization programmed death-ligand 1 (PD-L1) Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Priyanka Chauhan Wen S. Sheng Shuxian Hu Sujata Prasad James R. Lokensgard Differential Cytokine-Induced Responses of Polarized Microglia
description	The role of select pro- and anti-inflammatory mediators in driving microglial cell polarization into classically (M1), or alternatively, (M2) activated states, as well as the subsequent differential responses of these induced phenotypes, was examined. Expression of PD-L1, MHC-II, MHC-I, arginase 1 (Arg-1), and inducible nitric oxide synthase (iNOS) was assessed using multi-color flow cytometry. We observed that both pro- and anti-inflammatory mediators induced PD-L1 expression on non-polarized microglia. Moreover, IFN-γ stimulated significant MHC class I and II expression on these cells. Interestingly, we observed that only IL-4 treatment induced Arg-1 expression, indicating M2 polarization. These M2 cells were refractory to subsequent depolarization and maintained their alternatively activated state. Furthermore, PD-L1 expression was significantly induced on these M2-polarized microglia after treatment with pro-inflammatory mediators, but not anti-inflammatory cytokines. In addition, we observed that only LPS induced iNOS expression in microglial cells, indicating M1 polarization. Furthermore, IFN-γ significantly increased the percentage of M1-polarized microglia expressing iNOS. Surprisingly, when these M1-polarized microglia were treated with either IL-6 or other anti-inflammatory cytokines, they returned to their non-polarized state, as demonstrated by significantly reduced expression of iNOS. Taken together, these results demonstrate differential responses of microglial cells to mediators present in dissimilar microenvironments.
format	article
author	Priyanka Chauhan Wen S. Sheng Shuxian Hu Sujata Prasad James R. Lokensgard
author_facet	Priyanka Chauhan Wen S. Sheng Shuxian Hu Sujata Prasad James R. Lokensgard
author_sort	Priyanka Chauhan
title	Differential Cytokine-Induced Responses of Polarized Microglia
title_short	Differential Cytokine-Induced Responses of Polarized Microglia
title_full	Differential Cytokine-Induced Responses of Polarized Microglia
title_fullStr	Differential Cytokine-Induced Responses of Polarized Microglia
title_full_unstemmed	Differential Cytokine-Induced Responses of Polarized Microglia
title_sort	differential cytokine-induced responses of polarized microglia
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/917a425cb0ef40cd92bcca0d27ca452f
work_keys_str_mv	AT priyankachauhan differentialcytokineinducedresponsesofpolarizedmicroglia AT wenssheng differentialcytokineinducedresponsesofpolarizedmicroglia AT shuxianhu differentialcytokineinducedresponsesofpolarizedmicroglia AT sujataprasad differentialcytokineinducedresponsesofpolarizedmicroglia AT jamesrlokensgard differentialcytokineinducedresponsesofpolarizedmicroglia
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Differential Cytokine-Induced Responses of Polarized Microglia

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