| Author |
Furfaro AL, Mancini P, Passalacqua M, Ortolan J, Ivaldo C, Tirendi S, Vernazza S, d'Abramo C, Giliberto L, Nitti M.
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| Abstract |
Neuroinflammation is recognized as a pivotal factor in promoting neurodegeneration. However, the molecular mechanisms underlying the dysregulation of proinflammatory signaling in microglial cells remain largely elusive. A prominent role has been ascribed to the TLR4 receptor and its downstream targets, among which the transcription factor IRF5 has recently gained attention. Furthermore, the enzyme HO-1 is known to play a crucial role in mediating an anti-inflammatory phenotype in microglia. This study aims to investigate whether IRF5 is a target of the anti-inflammatory activity of HO-1. Using the human microglial cell line HMC3 and validating the results in RAW264.7 macrophage-like cells, via RT-qPCR, Western blotting, and immunofluorescence, we demonstrated that HO-1 contributes to the resolution of LPS-induced proinflammatory activation. Notably, cell exposure to a pharmacological inhibitor of HO-1 increases IRF5 mRNA expression, while treatment with Hemin, able to increase HO-1 expression, significantly reduces IRF5 phosphorylation. This work suggests a possible crosstalk between HO-1 and IRF5, proposing new druggable molecular targets to counteract neuroinflammation.
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