Capping protein regulator and myosin 1 linker 3 regulates transcription of key cytokines in activated phagocytic cells. Academic Article uri icon

Overview

abstract

  • We have recently reported that capping protein regulator and myosin 1 linker 3 (CARMIL3), first identified as an oncofetal-like gene, is required for metastasis of breast and prostate cancer cells via regulating the actin cytoskeletal dynamics near the plasma membrane. Here, we demonstrate a novel function of CARMIL3 as an essential regulator of the transcription of several key proinflammatory cytokines in macrophages engulfing apoptotic cells and/or exposed to lipopolysaccharides (LPS). CARMIL3-deficient macrophages expressed strongly abrogated levels of interleukin (IL)-6, TNF-α, IL-1β and IL-23 in response to LPS, whereas IL-10 expression was enhanced. An RNA-seq analysis of CARMIL3-deficient and wild-type (WT) RAW264.7 cells stimulated with LPS revealed many differentially expressed genes, impacting several important inflammatory pathways. At the molecular level, CARMIL3 deficiency caused a strong impairment in LPS-activated nuclear factor-κB (NF-κB) signaling with decreased IKKα/β and IκBα phosphorylation and severely reduced p65 protein levels. This study uncovers a crucial role of CARMIL3 in impacting the balance between inflammation and tissue homeostasis via regulating major cytokines production in phagocytic cells.

publication date

  • November 24, 2020

Research

keywords

  • Cytokines
  • Macrophages
  • Microfilament Proteins
  • Signal Transduction
  • Transcription, Genetic

Identity

Scopus Document Identifier

  • 85097100581

Digital Object Identifier (DOI)

  • 10.1016/j.cellsig.2020.109848

PubMed ID

  • 33246003

Additional Document Info

volume

  • 78