Research articles
ScienceAsia 49 (2023):ID 653-660 |doi:
10.2306/scienceasia1513-1874.2023.066
Celastrol attenuates interleukin-8 release from LPS-activated
human monocytes and monocyte-derived macrophages by
inhibiting the NF-κB signalling pathway
Nipapan Malisorna,*, Wannapa Bootkotra, Thassapong Khamkhaia, Ammara Chaikana, Supawadee Seubsasanab
ABSTRACT: Interleukin-8 (IL-8), a potent neutrophil chemotactic factor, plays a critical role during inflammation.
IL-8 is produced primarily by several immune cell types upon lipopolysaccharide (LPS) stimulation by activating the
nuclear factor-?B (NF-?B) signalling pathway. NF-?B is an important transcription factor implicated in the inflammatory
response, and the NF-?B signalling pathway is a potential target for inhibition by anti-inflammatory compounds.
Celastrol has been shown to have therapeutic potential in treating many inflammatory diseases; however, there is little
information on its ability to attenuate IL-8 production in human monocytes and macrophages. Here, we determined
the effects of celastrol on LPS-induced IL-8 release and its molecular mechanism. Celastrol treatment significantly
reduced IL-8 release from LPS-activated human monocytes and monocyte-derived macrophages with IC50 values of
3.13 ? 0.03 ?M and 3.18 ? 0.05 ?M, respectively. Additionally, the inhibitory effect of celastrol on the production
of IL-8 was related to the modulation of IL-8 mRNA levels. Pre-treatment with celastrol significantly inhibited IKK,
I?B?, and p65 phosphorylation and also prevented I?B? degradation due to LPS activation. Collectively, these results
demonstrate that celastrol attenuates the release of IL-8 from LPS-activated human monocytes and monocyte-derived
macrophages and suggest that inhibition of NF-?B signalling activation is likely a mechanism for the attenuation. This
anti-inflammatory effect further highlights the therapeutic potential of celastrol.
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| a |
Faculty of Medicine, Thammasat University, Pathumthani 12121 Thailand |
| b |
Faculty of Medicine, Thammasat University, Pathumthani 12121 Thailand |
* Corresponding author, E-mail: mnipapan@tu.ac.th, dr.nipapan@gmail.com
Received 10 Aug 2022, Accepted 8 May 2023
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