AI Article Synopsis
- High-mobility group box 1 (HMGB1) is a protein that plays a role in immune responses during infections, particularly concerning Mycoplasma gallisepticum (MG) infection.
- The study found that HMGB1 is released from macrophage nuclei during MG infection, leading to the activation of TLR2 and the NF-κB pathway, which causes severe inflammation.
- Treatments like ethyl pyruvate and glycyrrhizic acid can inhibit HMGB1 release and may help reduce immune organ damage in MG-infected chickens, suggesting that targeting HMGB1 could be a new strategy for treating chronic respiratory diseases.
Article Abstract
High-mobility group box 1 (HMGB1), a member of damage-associated molecular patterns (DAMPs), is involved in the immune regulation of several infectious diseases. (MG) infection is proved to cause an abnormal immune response, but the role of HMGB1 in MG-induced chronic respiratory disease (CRD) is unclear. In this study, we found that HMGB1 was released from the nucleus to the extracellular in macrophages upon infection with MG. Extracellular HMGB1 bound to TLR2 activating the NF-κB pathway triggering a severe inflammatory storm and promoting the progression of MG infection. More importantly, TLR4 could be activated by HMGB1 to trigger immune disorders after TLR2 was silenced. This disease process could be interrupted by ethyl pyruvate (EP) inhibition of HMGB1 release or glycyrrhizic acid (GA). Furthermore, treatment of MG-infected chickens with GA significantly alleviated immune organ damage. In conclusion, we demonstrate that HMGB1 is secreted extracellularly to form an inflammatory environment upon MG infection, triggering a further cellular inflammatory storm in a positive feedback approach. Blocking MG-induced HMGB1 release or suppression downstream of the HMGB1-TLR2/TLR4 axis may be a promising novel strategy for the treatment of CRD. Furthermore, this study may provide a theoretical reference for understanding non-LPS-activated TLR4 events.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9496866 | PMC |
| http://dx.doi.org/10.3390/cells11182817 | DOI Listing |
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