2. Academic Validation
  3. RANKL up-regulated by progesterone aggravates lipopolysaccharide-induced acute lung injury during pregnancy

RANKL up-regulated by progesterone aggravates lipopolysaccharide-induced acute lung injury during pregnancy

  • J Reprod Immunol. 2023 Feb:155:103788. doi: 10.1016/j.jri.2022.103788.
Zhen-Zhen Lai 1,  Wen-Jie Zhou 2,  Jia-Wei Shi 3,  Yu-Han Meng 4,  Jiang-Nan Wu 5,  Jiang-Feng Ye 6,  Ting Peng 7,  Chang-En Xu 8,  Ming-Qing Li 9
Affiliations

Affiliations

  • 1 Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Shanghai Medical School, Fudan University, Shanghai 200080, People's Republic of China; NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University, Shanghai 201203, People's Republic of China.
  • 2 Center of Reproductive Medicine of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China.
  • 3 Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Shanghai Medical School, Fudan University, Shanghai 200080, People's Republic of China.
  • 4 Center of Reproductive Medicine, Affiliated Hospital of Weifang Medical University, Weifang 261035, People's Republic of China.
  • 5 Clinical Epidemiology, Hospital of Obstetrics and Gynecology, Shanghai Medical School, Fudan University, Shanghai 200011, People's Republic of China.
  • 6 Institute for Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138632, Singapore.
  • 7 Department of Obstetrics, Hospital of Obstetrics and Gynecology, Shanghai Medical School, Fudan University, Shanghai 200011, People's Republic of China. Electronic address: [email protected].
  • 8 Department of Obstetrics, Hospital of Obstetrics and Gynecology, Shanghai Medical School, Fudan University, Shanghai 200011, People's Republic of China. Electronic address: [email protected].
  • 9 Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Shanghai Medical School, Fudan University, Shanghai 200080, People's Republic of China; NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University, Shanghai 201203, People's Republic of China; State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200433, People's Republic of China. Electronic address: [email protected].
PMID: 36580846 DOI: 10.1016/j.jri.2022.103788
Abstract

Acute lung injury (ALI) is a common acute respiratory disease with high morbidity and mortality rate in pregnant women. Receptor activator of NF-κB ligand (TNFSF11, also known as RANKL) exerts either pro-inflammatory or anti-inflammatory effects on the immune response. LPS administration reduced the survival time (n = 10, p < 0.01), increased wet/dry ratio (n = 10, p < 0.001) and lung injury score (n = 10, p < 0.001), the elevated proportions of plasmacytoid dendritic cells (pDCs) (n = 10, p < 0.0001), tissue-resident DCs (resDCs) (n = 10, p < 0.0001), macrophages (n = 10, p < 0.0001), and neutrophils (n = 10, p < 0.0001), and the expressions of costimulatory molecules and inflammation cytokines (n = 10, p < 0.05) in lungs of pregnant mice, compared with non-pregnant mice. In vitro, progesterone up-regulated the expression of RANKL (n > 6, p < 0.05) on pulmonary fibroblasts. The results of cytokine arrays showed that the cytokines associated with inflammatory response and leukocyte differentiation were decreased in pulmonary fibroblasts after treatment with anti-RANKL neutralizing antibody, compared with control pulmonary fibroblasts. More notably, we found that Tnfsf11-/- pregnant mice had longer survival durations (n = 10, p < 0.01), lower lung injury scores (n = 10, p < 0.05), and lower immune cell infiltration (n = 10, p < 0.05). These data imply that the RANKL/RANK axis plays an essential role in LPS-induced ALI during pregnancy possibly through a variety of pathways.

Keywords

Acute lung injury; Dendritic cells; Pregnancy; Progesterone; RANK; RANKL.

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