Inhibition of the MyD88 signaling pathway could upregulates Ghrelin expression to synergistically regulate hepatic -infected progression.

Introduction: AE and whether the inhibition of the MyD88 inflammatory pathway can enhance Ghrelin expression to collaboratively modulate AE progression remains unclear.

Methods: In this study, we evaluated Ghrelin serum levels and changes in TLR4/MyD88/NF-κB pathway proteins and inflammatory factors in AE patients and mouse models at different stages of infection (-4, -8, and -12 weeks). Additionally, we administered the MyD88 inhibitor TJ-M2010-5 intraperitoneally to infected mice to evaluate alterations in inflammation and Ghrelin levels, as well as disease progression.

Results: A decrease in serum Ghrelin levels in AE patients, whereas both Ghrelin and GHSR, along with TLR4/MyD88/NF-κB pathway proteins and markers of M1/M2 macrophage polarization, exhibited increased expression in the inflammatory cell zones surrounding hepatic lesions. Similar findings were observed in -infected mice. M1-type inflammatory expression predominated throughout the infection's progression, with sustained high levels of Ghrelin counteracting inflammation. The TLR4/ MyD88/NF-κB pathway remained suppressed during the first 8 weeks, becoming activated only at 12 weeks. Inhibition of the MyD88 pathway resulted in reduced inflammation levels and upregulated Ghrelin expression, thereby collaboratively regulating the progression of hepatic infection.

Conclusion: These findings suggest an interactive regulation between the MyD88 inflammatory signaling pathway and Ghrelin, indicating that MyD88 inhibition could enhance Ghrelin expression to modulate the progression of infection.