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ROS/TNF-α Crosstalk Triggers the Expression of IL-8 and MCP-1 in Human Monocytic THP-1 Cells via the NF-κB and ERK1/2 Mediated Signaling
| Content Provider | MDPI |
|---|---|
| Author | Akhter, Nadeem Wilson, Ajit Thomas, Reeby Al-Rashed, Fatema Kochumon, Shihab Al-Roub, Areej Arefanian, Hossein Al-Madhoun, Ashraf Al-Mulla, Fahd Ahmad, Rasheed Sindhu, Sardar |
| Copyright Year | 2021 |
| Description | IL-8/MCP-1 act as neutrophil/monocyte chemoattractants, respectively. Oxidative stress emerges as a key player in the pathophysiology of obesity. However, it remains unclear whether the TNF-α/oxidative stress interplay can trigger IL-8/MCP-1 expression and, if so, by which mechanism(s). IL-8/MCP-1 adipose expression was detected in lean, overweight, and obese individuals, 15 each, using immunohistochemistry. To detect the role of reactive oxygen species (ROS)/TNF-α synergy as a chemokine driver, THP-1 cells were stimulated with TNF-α, with/without $H_{2}O_{2}$ or hypoxia. Target gene expression was measured by qRT-PCR, proteins by flow cytometry/confocal microscopy, ROS by DCFH-DA assay, and signaling pathways by immunoblotting. IL-8/MCP-1 adipose expression was significantly higher in obese/overweight. Furthermore, IL-8/MCP-1 mRNA/protein was amplified in monocytic cells following stimulation with TNF-α in the presence of $H_{2}O_{2}$ or hypoxia (p ˂ 0.0001). Synergistic chemokine upregulation was related to the ROS levels, while pre-treatments with NAC suppressed this chemokine elevation (p ≤ 0.01). The ROS/TNF-α crosstalk involved upregulation of CHOP, ERN1, HIF1A, and NF-κB/ERK-1,2 mediated signaling. In conclusion, IL-8/MCP-1 adipose expression is elevated in obesity. Mechanistically, ROS/TNF-α crosstalk may drive expression of these chemokines in monocytic cells by inducing ER stress, HIF1A stabilization, and signaling via NF-κB/ERK-1,2. NAC had inhibitory effect on oxidative stress-driven IL-8/MCP-1 expression, which may have therapeutic significance regarding meta-inflammation. |
| Starting Page | 10519 |
| e-ISSN | 14220067 |
| DOI | 10.3390/ijms221910519 |
| Journal | International Journal of Molecular Sciences |
| Issue Number | 19 |
| Volume Number | 22 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2021-09-29 |
| Access Restriction | Open |
| Subject Keyword | International Journal of Molecular Sciences Immunology Ros Tnf-α Il-8 Cxcl8 Mcp-1 Ccl2 Oxidative Stress Meta-inflammation Obesity |
| Content Type | Text |
| Resource Type | Article |
