Coordinated Transcriptional Waves Define the Inflammatory Response of Primary Microglial Culture

Keren Zohar, Elyad Lezmi, Fanny Reichert, Tsiona Eliyahu, Shlomo Rotshenker, Marta Weinstock, Michal Linial

Research output: Contribution to journalArticlepeer-review

Abstract

The primary role of microglia is to maintain homeostasis by effectively responding to various disturbances. Activation of transcriptional programs determines the microglia’s response to external stimuli. In this study, we stimulated murine neonatal microglial cells with benzoyl ATP (bzATP) and lipopolysaccharide (LPS), and monitored their ability to release pro-inflammatory cytokines. When cells are exposed to bzATP, a purinergic receptor agonist, a short-lived wave of transcriptional changes, occurs. However, only combining bzATP and LPS led to a sustainable and robust response. The transcriptional profile is dominated by induced cytokines (e.g., IL-1α and IL-1β), chemokines, and their membrane receptors. Several abundant long noncoding RNAs (lncRNAs) are induced by bzATP/LPS, including Ptgs2os2, Bc1, and Morrbid, that function in inflammation and cytokine production. Analyzing the observed changes through TNF (Tumor necrosis factor) and NF-κB (nuclear factor kappa light chain enhancer of activated B cells) pathways confirmed that neonatal glial cells exhibit a distinctive expression program in which inflammatory-related genes are upregulated by orders of magnitude. The observed capacity of the microglial culture to activate a robust inflammatory response is useful for studying neurons under stress, brain injury, and aging. We propose the use of a primary neonatal microglia culture as a responsive in vitro model for testing drugs that may interact with inflammatory signaling and the lncRNA regulatory network.

Original languageAmerican English
Article number10928
JournalINTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume24
Issue number13
DOIs
StatePublished - Jul 2023

Keywords

  • RNA-seq
  • TNF signaling
  • cytokines
  • inflammation
  • innate immune system
  • interleukin
  • ncRNA
  • purinergic receptor

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Spectroscopy
  • Catalysis
  • Inorganic Chemistry
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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