Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

3-Iodothyronamine (T1AM) Reduces Inflammatory Response in Human Microglial HMC3 Cell Line

Version 1 : Received: 26 May 2023 / Approved: 29 May 2023 / Online: 29 May 2023 (09:35:35 CEST)

A peer-reviewed article of this Preprint also exists.

Polini, B.; Ricardi, C.; Bertolini, A.; Carnicelli, V.; Rutigliano, G.; Saponaro, F.; Zucchi, R.; Chiellini, G. T1AM/TAAR1 System Reduces Inflammatory Response and β-Amyloid Toxicity in Human Microglial HMC3 Cell Line. Int. J. Mol. Sci. 2023, 24, 11569. Polini, B.; Ricardi, C.; Bertolini, A.; Carnicelli, V.; Rutigliano, G.; Saponaro, F.; Zucchi, R.; Chiellini, G. T1AM/TAAR1 System Reduces Inflammatory Response and β-Amyloid Toxicity in Human Microglial HMC3 Cell Line. Int. J. Mol. Sci. 2023, 24, 11569.

Abstract

Microglial dysfunction is one of the hallmarks and leading causes of common neurodegenerative diseases (NDD), including Alzheimer’s disease (AD) and Parkinson’s disease (PD). All these pathologies are characterized by aberrant aggregation of disease-causing proteins in the brain, which can directly activate microglia, trigger microglia-mediated neuroinflammation, and increase oxidative stress. Inhibition of glial activation may represent a therapeutic target to alleviate neurodegeneration. Recently, 3-iodothyronamine (T1AM), an endogenous derivative of thyroid hormone (TH) able to interact directly with a specific GPCR known as trace amine-associated receptor 1 (TAAR1), gained interest for its ability to promote neuroprotection in several models. Nevertheless, T1AM’s effects on microglial disfunction remain still elusive. In the present work we investigated whether T1AM could inhibit the inflammatory response of human HMC3 microglial cells to LPS/TNFα or β-amyloid peptide 25-35 (Aβ25-35) stimuli. The results of ELISA and qPCR assays revealed that T1AM was able to reduce microglia-mediate inflammatory response by inhibiting the release of proinflammatory factors, including IL-6, TNFα, NF-kB, MCP1 and MIP1, while promoting the release of anti-inflammatory mediators, such as IL-10. Notably, T1AM anti-inflammatory action in HMC3 cells resulted to be a TAAR1-mediated response, further increasing the relevance of the T1AM/TAAR1 system in the management of NDD.

Keywords

neurodegeneration; microglia; inflammation; neuroprotection; trace-amine associated receptors type 1 (TAAR1); 3-iodothyronamine

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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