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LIF Aggravates Pulpitis by Promoting Inflammatory Response in Macrophages

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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.

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Acknowledgements

Thanks to the Key Laboratory of Oral Biomedicine Ministry of Education and Hubei Key Laboratory of Stomatology for providing us with the laboratory.

Funding

This study was financially supported by the National Natural Science Foundation of China (Nos. 82071090 and 82001014), the Innovation and Development Fund of Hubei Province Natural Science Foundation (No. 2022CFD005), Hubei Provincial Natural Science Foundation (No. 2022CFB115), and Shenzhen Scientific Research Project (No. JCYJ20180302144621755).

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Authors and 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

    Donghua Guo, Wei Dong, Yaqi Cong, Jiali Zhang & Yi Zhou

  2. Department of Stomatology, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi, China

    Yi Liu

  3. Yantian Hospital, Southern University of Science and Technology, Shenzhen, China

    Youde Liang

  4. Applied Oral Sciences and Community Dental Care, Faculty of Dentistry, The University of Hong Kong, Hong Kong, S.A.R, China

    Zhou Ye

  5. Center for Prosthodontics and Implant Dentistry, Optics Valley Branch, School and Hospital of Stomatology, Wuhan University, Wuhan, China

    Yi Zhou

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  1. Donghua Guo
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Contributions

Donghua Guo contributed to conceptualization, methodology, writing—original draft, visualization, and data curation. Wei Dong participated in methodology, validation, and discussion. Jiali Zhang and Yi Zhou participated in writing—review and editing, supervision, and discussion. Yaqi Cong, Yi Liu, Youde Liang, and Zhou Ye participated in the implementation of some experiments and discussion. All authors read and approved the final manuscript.

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Correspondence to Yi Zhou.

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All animal experiment was approved by the Institutional Animal Care and Use Committee of Wuhan University (approval no: S07923020D).

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Guo, D., Dong, W., Cong, Y. et al. LIF Aggravates Pulpitis by Promoting Inflammatory Response in Macrophages. Inflammation 47, 307–322 (2024). https://doi.org/10.1007/s10753-023-01910-6

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