Evaluation of TNF-α and IFN-γ primed conditioned medium of mesenchymal stem cell in acetic acid-induced mouse model of acute colitis

Cell Immunol. 2024 Nov-Dec:405-406:104876. doi: 10.1016/j.cellimm.2024.104876. Epub 2024 Sep 24.

Abstract

IBD, an autoimmune-inflammatory disorder that affects people who are genetically prone to inflammation. There is a lot of interest in MSC-CM therapy, especially when primed with TNF-α + IFN-γ. Throughout the study, data were collected on the percentage of apoptotic cells, gene expression of ZO-1, Foxp3, GATA3, IDO-1, Muc2, T-bet, Notch1, TNFR2, and ROR-γt, colon weight and length, histopathological analysis, and DAI. TNF-α and IL-10 levels were assessed in addition to the NO level. The results suggest that primed MSC-CM improved DAI, mucosal deterioration, intestinal inflammation and NO concentration. The amount of TNF-α was decreased, but IL-10 and the colon's percentage of apoptotic cells was increased. The mRNA expression of ZO-1, Foxp3, GATA3, IDO-1, and Muc2 genes increased greatly in the treatment groups, while the expression of T-bet, Notch1, TNFR2, and ROR-γt genes has decreased. These studies suggest that primed MSC-CM may combine with common treatments to improve responsiveness.

Keywords: Acetic acid; Colitis; Conditioned medium; IFN-γ; Mesenchymal stem cell; TNF-α.

MeSH terms

  • Acute Disease
  • Animals
  • Apoptosis / drug effects
  • Colitis* / chemically induced
  • Colitis* / metabolism
  • Colon / metabolism
  • Colon / pathology
  • Culture Media, Conditioned / pharmacology
  • Disease Models, Animal*
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • GATA3 Transcription Factor* / genetics
  • GATA3 Transcription Factor* / metabolism
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / genetics
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
  • Interferon-gamma* / metabolism
  • Interferon-gamma* / pharmacology
  • Interleukin-10 / metabolism
  • Male
  • Mesenchymal Stem Cells* / metabolism
  • Mice
  • Mucin-2 / genetics
  • Mucin-2 / metabolism
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
  • Receptor, Notch1 / genetics
  • Receptor, Notch1 / metabolism
  • T-Box Domain Proteins* / genetics
  • T-Box Domain Proteins* / metabolism
  • Tumor Necrosis Factor-alpha* / metabolism
  • Zonula Occludens-1 Protein / genetics
  • Zonula Occludens-1 Protein / metabolism

Substances

  • Interferon-gamma
  • Tumor Necrosis Factor-alpha
  • GATA3 Transcription Factor
  • T-box transcription factor TBX21
  • Culture Media, Conditioned
  • T-Box Domain Proteins
  • Foxp3 protein, mouse
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Interleukin-10
  • Gata3 protein, mouse
  • Forkhead Transcription Factors
  • Mucin-2
  • Zonula Occludens-1 Protein
  • Tjp1 protein, mouse
  • Muc2 protein, mouse
  • IDO1 protein, mouse
  • Notch1 protein, mouse
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Receptor, Notch1