Potential role of ghrelin in the regulation of inflammation

• Published in: The FASEB journal 2022-09, Vol.36 (9), p.e22508-n/a
• Main Authors: Ma, Yunxiao, Zhang, Haifeng, Guo, Weiying, Yu, Lu
• Format: Article
• Language: English
• Subjects: disease; ghrelin; GHS‐R1a; inflammation; NF‐κB
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.202200634R

Several diseases are caused or progress due to inflammation. In the past few years, accumulating evidence suggests that ghrelin, a gastric hormone of 28‐amino acid residue length, exerts protective effects against inflammation by modulating the related pathways. This review focuses on ghrelin's anti‐inflammatory and potential therapeutic effects in neurological, cardiovascular, respiratory, hepatic, gastrointestinal, and kidney disorders. Ghrelin significantly alleviates excessive inflammation and reduces damage to different target organs mainly by reducing the secretion of inflammatory cytokines, including interleukin‐6 (IL‐6), interleukin‐1β (IL‐1β), and tumor necrosis factor‐α (TNF‐α), and inhibiting the nuclear factor kappa‐B (NF‐κB) and NLRP3 inflammasome signaling pathways. Ghrelin also regulates inflammation and apoptosis through the p38 MAPK/c‐Jun N‐terminal kinase (JNK) signaling pathway; restores cerebral microvascular integrity, and attenuates vascular leakage. Ghrelin activates the phosphoInositide‐3 kinase (PI3K)/protein kinase B (Akt) pathway and inhibits inflammatory responses in cardiovascular diseases and acute kidney injury. Some studies show that ghrelin exacerbates colonic and intestinal manifestations of colitis. Interestingly, some inflammatory states, such as non‐alcoholic steatohepatitis, inflammatory bowel diseases, and chronic kidney disease, are often associated with high ghrelin levels. Thus, ghrelin may be a potential new therapeutic target for inflammation‐related diseases.