Suppression of TLR4 dimerization by terahertz irradiation inhibits LPS-induced inflammation: A molecular dynamics...

Toll-like receptor 4 (TLR4) plays a pivotal role in the innate immune system by recognizing lipopolysaccharide (LPS) and triggering inflammatory signaling pathways. Previous studies have shown that 0.1 THz irradiation can alleviate LPS-induced inflammation, but the specific mechanisms underlying this effect remain unclear. This study investigated the anti-inflammatory role of 0.1 THz irradiation by exploring its impact on TLR4 dimerization and LPS-induced inflammatory responses, using molecular dynamics simulations combined with in vitro validation. Results demonstrated that 0.1 THz irradiation significantly reduced the expression of TLR4 and its downstream signaling molecule MyD88 in LPS-stimulated HaCaT cells, inhibited the degradation of IκBα and phosphorylation of p65, and crucially suppressed LPS-induced TLR4 dimerization. This suppression of TLR4 dimerization further blocked the activation of the NF-κB inflammatory pathway. Molecular dynamics simulations revealed that 0.1 THz irradiation induced structural alterations of the (TLR4/MD-2/LPS)₂ complex, disrupted TLR4 dimerization, and altered the hydrogen bond distribution between proteins and surrounding water molecules. These structural changes likely interfere with the conformational prerequisites required for TLR4 dimerization and the subsequent activation of downstream signaling. Our findings clarify that 0.1 THz irradiation exerts anti-inflammatory effects by inhibiting TLR4 dimerization and downstream inflammatory signaling, which provides novel insights into the anti-inflammatory mechanisms of THz irradiation. This study also highlights the potential of terahertz technology as a promising strategy for the intervention and management of skin inflammatory.