Immunomodulation via MyD88-NFκB Signaling Pathway from Human Umbilical Cord-Derived Mesenchymal Stem Cells in Acute Lung Injury

• Published in: International journal of molecular sciences Vol. 23; no. 10; p. 5295
• Main Authors: Wu, Kang-Hsi, Li, Ju-Pi, Chao, Wan-Ru, Lee, Yi-Ju, Yang, Shun-Fa, Cheng, Ching-Chang, Chao, Yu-Hua
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 10.05.2022; MDPI
• Subjects: Acute Lung Injury - metabolism; Acute Lung Injury - therapy; Animals; Cytokine storm; Disease; Disease Models, Animal; Humans; Immunomodulation; Inflammation; Lungs; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - metabolism; Mice; Myeloid Differentiation Factor 88 - genetics; Myeloid Differentiation Factor 88 - metabolism; Neutrophils; NF-kappa B - metabolism; Permeability; Proteins; Signal Transduction; Stem cells; Tumor necrosis factor-TNF; Umbilical cord; Umbilical Cord - cytology; Umbilical Cord - metabolism; Toll-like receptors; myeloid differentiation factor 88; immunomodulation; acute lung injury; mesenchymal stem cells
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23105295

Excess inflammatory processes play a key detrimental role in the pathophysiology of acute lung injury (ALI). Mesenchymal stem cells (MSCs) were reported to be beneficial to ALI, but the underlying mechanisms have not been completely understood. The present study aimed to examine the involvement of MyD88–NFκB signaling in the immunomodulation of MSCs in mice with lipopolysaccharides (LPS)-induced ALI. We found that serum concentrations of IL-6, TNF-α, MCP-1, IL-1β, and IL-8 were significantly decreased at 6 h after LPS-induced ALI in the MSC group (p < 0.05). For each of the five cytokines, the serum concentration of each individual mouse in either group declined to a similar level at 48 h. The intensity of lung injury lessened in the MSC group, as shown by histopathology and lung injury scores (p < 0.001). The expressions of MyD88 and phospho-NFκB in the lung tissue were significantly decreased in mice receiving MSCs as measured by Western blotting and immunohistochemistry. Our data demonstrated that human umbilical cord-derived MSCs could effectively alleviate the cytokine storm in mice after LPS-induced ALI and attenuated lung injury. Firstly, we documented the correlation between the down-regulation of MyD88–NFκB signaling and immunomodulatory effects of MSCs in the situation of ALI.