TNF-α stimulation under oxidative stress augments the expression of monocyte chemoattractant protein (MCP)-1 in THP-1 cells via the NF-κB/ERK1-2 mediated signaling

Research output: Contribution to conferencePosterpeer-review

Abstract

MCP-1 (CCL2) is a central chemokine that regulates the migration and infiltration of monocytes/ macrophages and it is found to be upregulated in obesity/ type-2 diabetes. In metabolic conditions, MCP-1 is concomitantly expressed with TNF-α. It is unclear whether oxidative stress, as from hypoxic milieu in the adipose tissue, plays a role to promote MCP-1 expression by monocytic cells in presence of TNF-α and exacerbate inflammation. To test the hypothesis, THP-1 monocytic cells were stimulated with TNF-α, in presence or absence of H2O2 or incubation under 1% hypoxia (mimicking oxidative stress). MCP-1, CHOP, ERN1, and HIF-1α mRNA expression was assessed by qRT-PCR; MCP-1 protein expression was measured by flow cytometry or immunohistochemistry; NF-κB and ERK-1/2 phosphorylation was detected by western blotting; and ROS expression was determined by DCFH-DA assay. The data show that MCP-1 mRNA/ protein expression was significantly elevated in THP-1 cells stimulated with TNF-α and H2O2 or 1% hypoxia. Increased MCP-1 expression was associated with induced ROS levels, expression of CHOP, ERN1, HIF-1α, and phosphorylation of NF-κB/ERK1-2. The synergistic MCP-1 expression was abrogated by pre-treating cells with N-acetyl cysteine or curcumin (P<0.01). In conclusion, ROS-induction amplifies MCP-1 expression in TNF-α-stimulated THP-1 cells via the molecular mechanisms involving ER stress, HIF-1α stabilization, and NF-κB/ERK1-2 mediated signaling, which may have significance for metabolic inflammation.
Original languageEnglish
Publication statusPublished - 2021
EventKeystone symposia: Integrating metabolism and immunity (EK16) - , United States
Duration: 25 Jan 202128 Jan 2021

Conference

ConferenceKeystone symposia
Country/TerritoryUnited States
Period25/01/2128/01/21

Keywords

  • Oxidative stress
  • TNF-α
  • MCP-1
  • CCL2
  • NF-κB
  • ERK1/2
  • Monocytic cells

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