Herbal melanin induces interleukin‑1β secretion and production by human THP‑1 monocytes via Toll‑like receptor 2 and p38 MAPK activation

El‑Obeid,Adila; Yahya,Wesam Bin; Almuzzaini,Bader; Tuwaijri,Abeer Al; Najdi,Maria; Hassib,Adil; Matou‑Nasri,Sabine

doi:10.3892/etm.2021.10515

Herbal melanin induces interleukin‑1β secretion and production by human THP‑1 monocytes via Toll‑like receptor 2 and p38 MAPK activation

Authors:
- Adila El‑Obeid
- Wesam Bin Yahya
- Bader Almuzzaini
- Abeer Al Tuwaijri
- Maria Najdi
- Adil Hassib
- Sabine Matou‑Nasri
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Affiliations: Biobank, King Abdullah International Medical Research Center, Riyadh 11481, Saudi Arabia, Cell and Gene Therapy Group, Medical Genomics Research Department, King Abdullah International Medical Research Center, Ministry of National Guard-Health Affairs, King Saud bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia, Medical Genomics Research Department, King Abdullah International Medical Research Center, Ministry of National Guard-Health Affairs; King Saud bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia, Department of Physics, Faculty of Science, University of Khartoum, Khartoum 11111, Sudan
Published online on: July 29, 2021 https://doi.org/10.3892/etm.2021.10515
Article Number: 1081
Copyright: © El‑Obeid et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Herbal melanin (HM), extracted from Nigella sativa, is known for its immunogenic properties through the modulation of cytokine production via Toll‑like receptor (TLR)4. TLRs play a crucial role in the host defense through the regulation of innate and adaptive immune responses. However, the potential effect of HM on the production of interleukin‑1β (IL‑1β), the main immunoregulatory cytokine secreted by activated monocytes, has not been reported. The present study aimed to investigate the effects of HM on IL‑1β secretion and production, detected by enzyme‑linked immunosorbent assay, western blotting and mRNA expression monitored by reverse transcription‑PCR, in human monocytes and a monocytic cell line, THP‑1. Signaling pathways involved in the HM‑induced IL‑1β production was investigated in the THP‑1 cells. It was shown that HM upregulated the IL‑1β mRNA in the THP‑1 cells and induced the secretion of IL‑1β in the monocytes and THP‑1 cells, in a dose‑dependent manner, compared to the untreated cells. HM increased the protein expression of IL‑1β, TLR2, the main receptor for IL‑1β production, and activated p38 mitogen‑activated protein kinase (MAPK), a key mediator for stress‑induced IL‑1β gene expression. The blockade of the p38 MAPK pathway, with the pharmacological inhibitor SB202190, and TLR2 receptor with a neutralization antibody, resulted in the decrease of HM‑induced IL‑1β production in THP‑1 cells. The TLR4 receptor blockade also decreased HM‑induced IL‑1β production, but to a lesser extent than TLR2 blockade. In conclusion, the present study demonstrated that HM stimulates IL‑1β production in monocytes and THP‑1 cells, in a TLR2/p38 MAPK pathway‑dependent manner, suggesting promising immunoregulatory potentials of HM against inflammatory‑associated diseases.

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