title: Decline in intestinal mucosal IL-10 expression and decreased intestinal barrier function in a mouse model of total parenteral nutrition.
abstract: Loss of intestinal epithelial barrier function (EBF) is a major problem associated with total parenteral nutrition (TPN) administration. We have previously identified intestinal intraepithelial lymphocyte (IEL)-derived interferon-gamma (IFN-gamma) as a contributing factor to this barrier loss. The objective was to determine whether other IEL-derived cytokines may also contribute to intestinal epithelial barrier breakdown. C57BL6J male mice received TPN or enteral nutrition (control) for 7 days. IEL-derived interleukin-10 (IL-10) was then measured. A significant decline in IEL-derived IL-10 expression was seen with TPN administration, a cytokine that has been shown in vitro to maintain tight junction integrity. We hypothesized that this change in IEL-derived IL-10 expression could contribute to TPN-associated barrier loss. An additional group of mice was given exogenous recombinant IL-10. Ussing chamber experiments showed that EBF markedly declined in the TPN group. TPN resulted in a significant decrease of IEL-derived IL-10 expression. The expression of several tight junction molecules also decreased with TPN administration. Exogenous IL-10 administration in TPN mice significantly attenuated the TPN-associated decline in zonula occludens (ZO)-1, E-cadherin, and occludin expression, as well as a loss of intestinal barrier function. TPN administration led to a marked decline in IEL-derived IL-10 expression. This decline was coincident with a loss of intestinal EBF. As the decline was partially attenuated with the administration of exogenous IL-10, our findings suggest that loss of IL-10 may be a contributing mechanism to TPN-associated epithelial barrier loss.
authors.affiliation: Department of Surgery, University of Michigan Medical School, Ann Arbor, MI 48109-0245, USA.
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Sun
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.forename: Keisuke
authors.initials: K
authors.lastname: Nose
authors.forename: Satoko
authors.initials: S
authors.lastname: Nose
authors.forename: Emir Q
authors.initials: EQ
authors.lastname: Haxhija
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Koga
authors.forename: Yongjia
authors.initials: Y
authors.lastname: Feng
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Teitelbaum
mesh_terms: D000818:Animals; D018988:Bacterial Translocation; D015820:Cadherins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D057167:Claudins; D015536:Down-Regulation; D017097:Electric Impedance; D016753:Interleukin-10 / Q000378:metabolism*; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000382:microbiology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D062793:Occludin; D010289:Parenteral Nutrition, Total; D010539:Permeability; D010750:Phosphoproteins / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D019108:Tight Junctions / Q000378:metabolism* / Q000382:microbiology; D062826:Zonula Occludens-1 Protein
chemical_list: D015820:Cadherins; D015815:Cell Adhesion Molecules; D057167:Claudins; C113371:Cldn2 protein, mouse; C507360:Cldn7 protein, mouse; C498686:F11r protein, mouse; D008565:Membrane Proteins; D062793:Occludin; C568986:Ocln protein, mouse; D010750:Phosphoproteins; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein; C459596:claudin 15; D016753:Interleukin-10