2. Academic Validation
  3. Melatonin attenuates lipopolysaccharide-induced immune dysfunction in dendritic cells

Melatonin attenuates lipopolysaccharide-induced immune dysfunction in dendritic cells

  • Int Immunopharmacol. 2023 Jul:120:110282. doi: 10.1016/j.intimp.2023.110282.
Tao Qin 1,  Danni Feng 2,  Bangyue Zhou 3,  Lirong Bai 3,  Shengjie Zhou 4,  Jiangtao Du 5,  Gang Xu 6,  Yinyan Yin 7
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu, China; Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yangzhou University, Yangzhou, Jiangsu, China. Electronic address: [email protected].
  • 2 College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China.
  • 3 College of Medicine, Yangzhou University, Yangzhou, Jiangsu, China.
  • 4 Clinical Medical College, Yangzhou University, Department of Burn and Plastic Surgery, Northern Jiangsu People's Hospital, Yangzhou, Jiangsu, China.
  • 5 Laboratory Animal Center, Hangzhou Medical College, Hangzhou, Zhejiang, China.
  • 6 Clinical Medical College, Yangzhou University, Department of Burn and Plastic Surgery, Northern Jiangsu People's Hospital, Yangzhou, Jiangsu, China. Electronic address: [email protected].
  • 7 College of Medicine, Yangzhou University, Yangzhou, Jiangsu, China; Guangling College, Yangzhou University, Yangzhou, Jiangsu, China. Electronic address: [email protected].
PMID: 37224647 DOI: 10.1016/j.intimp.2023.110282
Abstract

Melatonin, a ubiquitous hormone, is principally secreted from pineal gland in mammals and possesses strong antioxidant and anti-inflammatory properties. However, its specific roles in the immune functions of dendritic cells (DCs) during acute lung injury (ALI) remain unknown. In this study, we found that melatonin restored the body weight, decreased the lung weight/body weight ratio, alleviated the histopathological lung injury, and decreased the levels of cytokines (tumor necrosis factor-α (TNF-α), interleukin (IL)-12p70, IL-17, and IL-10) in bronchoalveolar lavage fluid of the lipopolysaccharide (LPS)-induced ALI murine model. Moreover, melatonin inhibited the major histocompatibility complex II (MHCII) expression of lung CD11b+ DCs after LPS challenge in vivo. In vitro, melatonin reversed the shape index, promoted the endocytosis, and inhibited phenotypic expression of MHCII, CD40, CD80, and CD86 in LPS-activated DCs. Furthermore, melatonin decreased the expression of an activated marker, CD69, and the secretion of pro-inflammatory cytokines (TNF-α, IL-12p70, and IL-17) after LPS challenge. It hampered the LPS-activated DCs migration by downregulating the C-C Chemokine Receptor 7 (CCR7) expression, and then weakened the ability of LPS-induced DCs to stimulate allogeneic CD4+ T cell proliferation. Melatonin shaped the immune function of DCs in a nuclear factor erythroid-2-related factor 2 (Nrf-2)/heme oxygenase-1 (HO-1) axis-dependent manner. These findings indicate that melatonin protects DCs from ALI-induced immunological stress and may be used to develop novel DC-targeting strategies for ALI therapy.

Keywords

Acute lung injury; Dendritic cells; Immunological stress; Melatonin.

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