G protein-coupled receptor 91 promotes the inflammatory response to Porphyromonas gingivalis in bone marrow-derived macrophages

Wenqi Su; Yujia Wang; Cancan Zu; Lang Lei; Houxuan Li

doi:10.1016/j.heliyon.2024.e34509

G protein-coupled receptor 91 promotes the inflammatory response to Porphyromonas gingivalis in bone marrow-derived macrophages

Heliyon. 2024 Jul 14;10(14):e34509. doi: 10.1016/j.heliyon.2024.e34509. eCollection 2024 Jul 30.

Authors

Wenqi Su^{1

2}, Yujia Wang^{1

2}, Cancan Zu^{1

2}, Lang Lei³, Houxuan Li¹

Affiliations

¹ Department of Periodontics, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing, China.
² Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing, China.
³ Department of Orthodontics, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing, China.

Abstract

Macrophages are important for maintaining tissue homeostasis and defending against pathogens in periodontal tissues. However, these tissues are often vulnerable to damage due to local inflammatory responses within the host tissues. This study aimed to investigate the role of G protein-coupled receptor 91(GPR91) during the inflammatory response to Porphyromonas gingivalis (P. gingivalis) in bone marrow-derived macrophages (BMDMs). To this end, we examined expression levels of GPR91 genes in human periodontal tissues affected by periodontitis. Utilizing primary mouse BMDMs from wild-type (WT) and GPR91 knockout (GPR91^-/-) mice infected with P. gingivalis, we demonstrated that GPR91 accumulates in inflamed gingival tissues. Additionally, P. gingivalis can induce intercellular succinate accumulation, inflammatory mediator generation, reactive oxygen species (ROS) production, lipid peroxidation, and superoxide dismutase activity in WT-BMDMs. Moreover, inhibition of GPR91 by the specific inhibitor 4C as well as knockdown of GPR91 reduced inflammation and oxidative stress in P. gingivalis-infected BMDMs. Furthermore, we discovered that GPR91-mediated inflammation in P. gingivalis-infected BMDMs is activated via the Erk/Nuclear Factor-κB pathway. These findings provide new insights into the metabolic pathogenesis of periodontal inflammation.

Keywords: Bone marrow-derived macrophages; GPR91; Nuclear factor-κB; P. gingivalis; Periodontitis; Succinate.