2. Academic Validation
  3. LIF Aggravates Pulpitis by Promoting Inflammatory Response in Macrophages

LIF Aggravates Pulpitis by Promoting Inflammatory Response in Macrophages

  • Inflammation. 2023 Oct 2. doi: 10.1007/s10753-023-01910-6.
Donghua Guo 1,  Wei Dong 1,  Yaqi Cong 1,  Yi Liu 2,  Youde Liang 3,  Zhou Ye 4,  Jiali Zhang 1,  Yi Zhou 5 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China.
  • 2 Department of Stomatology, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi, China.
  • 3 Yantian Hospital, Southern University of Science and Technology, Shenzhen, China.
  • 4 Applied Oral Sciences and Community Dental Care, Faculty of Dentistry, The University of Hong Kong, Hong Kong, S.A.R, China.
  • 5 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China. dryizhou@whu.edu.cn.
  • 6 Center for Prosthodontics and Implant Dentistry, Optics Valley Branch, School and Hospital of Stomatology, Wuhan University, Wuhan, China. dryizhou@whu.edu.cn.
PMID: 37782452 DOI: 10.1007/s10753-023-01910-6
Abstract

Leukemia Inhibitory Factor (LIF) has been recognized as a novel inflammatory modulator in inflammation-associated diseases. This study aimed to investigate the modulation of LIF in dental pulp inflammation. Experimental pulpitis was established in wild-type (WT) and Lif-deficient (Lif-/-) mice. Histological and immunostaining analyses were conducted to assess the role of LIF in the progression of pulpitis. Mouse macrophage cell line (RAW264.7) was treated with LPS to simulate an inflammatory environment. Exogenous LIF was added to this system to examine its modulation in macrophage inflammatory response in vitro. Primary bone marrow-derived macrophages (BMDMs) from WT and Lif-/- mice were isolated and stimulated with LPS to confirm the effect of Lif deletion on macrophage inflammatory response. Supernatants from LIF and LPS-treated human dental pulp cells (hDPCs) were collected and added to macrophages. Macrophage chemotaxis was assessed using transwell assays. The results showed an increased expression of LIF and LIFR with the progression of pulpitis, and LIFR was highly expressed in macrophages. Lif deficiency alleviated experimental pulpitis with the reduction of pro-inflammatory cytokines and macrophage infiltration. Exogenous LIF promoted inflammatory response of LPS-induced macrophages through a STAT3/p65-dependent pathway. Consistently, Lif deletion inhibited macrophage inflammatory response in vitro. Supernatants of LIF-treated hDPCs enhanced macrophage migration in LPS-induced inflammatory environment. Our findings demonstrated that LIF aggravates pulpitis by promoting macrophage inflammatory response through a STAT3/p65-dependent pathway. Furthermore, LIF plays a crucial role in driving the recruitment of macrophages to inflamed pulp tissue by promoting chemokine secretion in DPCs.

Keywords

Inflammation; Leukemia inhibitory factor; Macrophage; Pulpitis.

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