1. Academic Validation
  2. HIPK2 sustains inflammatory cytokine production by promoting endoplasmic reticulum stress in macrophages

HIPK2 sustains inflammatory cytokine production by promoting endoplasmic reticulum stress in macrophages

  • Exp Ther Med. 2020 Dec;20(6):171. doi: 10.3892/etm.2020.9301.
Long Xu 1 He Fang 1 Dayuan Xu 1 Guangyi Wang 1
Affiliations

Affiliation

  • 1 Center of Burns and Trauma, Changhai Hospital, Naval Medical University, Shanghai 200433, P.R. China.
Abstract

Uncontrolled inflammatory cytokine production by macrophages contributes to numerous conditions, including Infection, endotoxemia and sepsis. A previous study proposed that endoplasmic reticulum (ER) stress acts as an essential process in inflammatory cytokine production by macrophages. The present study used a mouse sepsis model and in vitro macrophages to demonstrate that homeodomain-interacting protein kinase 2 (HIPK2) sustained cytokine production in an ER stress-dependent manner. HIPK2 expression was upregulated in the early phase of lipopolysaccharide stimulation. HIPK2 knockdown attenuated IL-6 and TNF-α production, and p65 phosphorylation in macrophages. Furthermore, the attenuated cytokine production was abolished by the ER stress agonist tunicamycin. The activation of ER stress increased the levels of IL-6 and TNF-α, and the phosphorylation of p65, in macrophages following knockdown of HIPK2. Furthermore, HIPK2 inhibition attenuated the production of IL-6 and TNF-α in vitro and in vivo. Therefore, HIPK2 sustained inflammatory cytokine production by promoting ER stress in macrophages. Targeting HIPK2 may be a potential strategy for the management of uncontrolled inflammation in clinical settings.

Keywords

IL-6; TNF-α; homeodomain-interacting protein kinase 2; inflammation; macro-phage.

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