title: Transforming growth factor-β1 regulated phosphorylated AKT and interferon gamma expressions are associated with epithelial cell survival in rhesus macaque colon explants.
abstract: Transforming growth factor-β1 (TGF-β1) is an important immunoregulatory cytokine that plays an obligate role in regulating T-cell functions. Here, we demonstrated the role of TGF-β1 in regulating the survival of intestinal epithelial cells (ECs) in rhesus colon explant cultures using either anti-TGF-β1 antibody or recombinant TGF-β1 proteins. Neutralization of endogenous TGF-β1 using anti-TGF-β1 antibodies induced apoptosis of both intestinal ECs and lamina propria (LP) cells. Additionally, endogenous TGF-β1 blocking significantly increased expression of IFNγ, TNFα, CD107a and Perforin in LP cells compared to media and isotype controls. A significant decrease in pAKT expression was detected in anti-TGF-β1 MAbs treated explants compared to isotype and rTGF-β1 protein treated explants. Our results demonstrated TGF-β1 regulated pAKT and IFNγ expressions were associated with epithelial cell survival in rhesus macaque colon explants and suggest a potential role of mucosal TGF-β1 in regulating intestinal homeostasis and EC integrity.
authors.affiliation: Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA, USA; Tulane University School of Medicine, New Orleans, LA, USA. Electronic address: bpahar@tulane.edu.
authors.forename: Bapi
authors.initials: B
authors.lastname: Pahar
authors.affiliation: Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA, USA.
authors.forename: Diganta
authors.initials: D
authors.lastname: Pan
authors.affiliation: Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA, USA.
authors.forename: Wendy
authors.initials: W
authors.lastname: Lala
authors.affiliation: Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA, USA.
authors.forename: Carys S
authors.initials: CS
authors.lastname: Kenway-Lynch
authors.affiliation: Division of Microbiology, Tulane National Primate Research Center, Covington, LA, USA.
authors.forename: Arpita
authors.initials: A
authors.lastname: Das
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D007371:Interferon-gamma / Q000187:drug effects / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D008253:Macaca mulatta; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D053773:Transforming Growth Factor beta1; D007371:Interferon-gamma; D051057:Proto-Oncogene Proteins c-akt
keywords: Apoptosis; Colon; Epithelial cell; Rhesus macaque; TGF-β1; pAKT