Anti-inflammatory effects of budesonide in intestinal epithelial cells.
The glucocorticosteroid budesonide is one of the mainstay treatments in inflammatory bowel disease. The aim of this study was to investigate its effects on Caco-2 cells upon coculture with LPS stimulated macrophages, or with conditioned medium (CM) from the same. The mRNA expression of the chemokines IL-8 and ENA-78 were upregulated in Caco-2 cells, which was always more pronounced in the coculture, as compared to the CM situation, with the ENA-78 induction being higher than of IL-8. Addition of budesonide to the apical side of Caco-2 cells, decreased both IL-8 and ENA-78 mRNA levels in a dose dependent manner. A reduction in trans epithelial electrical resistance (TEER) and an increase in the apical-basolateral transport of fluoresceinated sulfonic acid (FS) were observed in the Caco-2 cells both in cocultures and CM experiments. The reduction in TEER was counteracted by budesonide, whereas it had no effect on the FS transport. We conclude that budesonide exert an anti-inflammatory effect directly on intestinal epithelial cells, which may contribute to the overall action of budesonide in the treatment of inflammatory bowel diseases.
Fredin
Maria Fritsch
MF
Department of Integrative Pharmacology, AstraZeneca AB, R&D Mölndal, Mölndal, Sweden. Maria.fritsch@astrazeneca.com
Ulfhammer
Erik
E
Rhedin
Magdalena
M
Melgar
Silvia
S
Mellgård
Björn
B
Peterson
Anders
A
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D019819:Budesonide / Q000494:pharmacology*; D018938:Caco-2 Cells; D054365:Chemokine CXCL5; D019743:Chemokines, CXC / Q000235:genetics; D017097:Electric Impedance; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics; D007413:Intestinal Mucosa / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis
D000893:Anti-Inflammatory Agents; C486263:CXCL5 protein, human; D054365:Chemokine CXCL5; D019743:Chemokines, CXC; D016209:Interleukin-8; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D019819:Budesonide