Formyl peptide receptor 1 mitigates colon inflammation and maintains mucosal homeostasis through the inhibition of CREB-C/EBPβ-S100a8 signaling

Tingting Li; Xiaojun Zhou; Qian Zhang; Qi Miao; Owen L Woodman; Yuguo Chen; Chengxue Qin

doi:10.1016/j.mucimm.2024.04.001

Formyl peptide receptor 1 mitigates colon inflammation and maintains mucosal homeostasis through the inhibition of CREB-C/EBPβ-S100a8 signaling

Mucosal Immunol. 2024 Apr 15:S1933-0219(24)00038-2. doi: 10.1016/j.mucimm.2024.04.001. Online ahead of print.

Authors

Tingting Li¹, Xiaojun Zhou², Qian Zhang¹, Qi Miao¹, Owen L Woodman³, Yuguo Chen⁴, Chengxue Qin⁵

Affiliations

¹ Department of Pharmacology, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
² Department of Pharmacology, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China; Department of Endocrinology and Metabology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Institute of Nephrology, Jinan, China; Department of Endocrinology and Metabology, Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Institute of Nephrology, Shandong University, Jinan, China.
³ Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Australia.
⁴ Department of Emergency Medicine, Chest Pain Center, Qilu Hospital of Shandong University, Jinan, China; Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, China; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China.
⁵ Department of Pharmacology, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China; Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Australia; Department of Emergency Medicine, Chest Pain Center, Qilu Hospital of Shandong University, Jinan, China; Baker Heart and Diabetes Institute, Melbourne, Australia. Electronic address: Helena.qin@monash.edu.

PMID: 38614323
DOI: 10.1016/j.mucimm.2024.04.001

Abstract

Excessive inflammatory responses are the main characteristic of ulcerative colitis (UC). Activation of formyl peptide receptor 1 (FPR1) has been found to promote the proliferation and migration of epithelial cells, but its role and therapeutic potential in UC remain unclear. This study observed an increased expression of FPR1 in a mouse model of colitis. Interestingly, FPR1 deficiency exacerbated UC and increased the secretion of the proinflammatory mediator from immune cells (e.g. macrophages), S100a8, a member of the damage-associated molecular patterns. Notably, the administration of the FPR agonist Cmpd43 ameliorated colon injury in a preclinical mice model of UC, likely via inhibiting phosphorylation of cyclic adenosine monophosphate-response element-binding protein and expression of CCAAT/enhancer-binding protein β, which in turn suppressed the secretion of S100a8. In conclusion, these findings discovered a novel role of FPR1 in the development of colitis and will facilitate the development of FPR1-based pharmacotherapy to treat UC.