GM-CSF, IL-1α, IL-1β, IL-6, IL-8, IL-10, ICAM-1 and VCAM-1 gene expression and cytokine production in human duodenal fibroblasts stimulated with lipopolysaccharide, IL-1α and TNF-α

• Published in: Clinical and experimental immunology Vol. 96; no. 3; pp. 437 - 443
• Main Authors: PANG, G, COUCH, L, BATEY, R, CLANCY, R, CRIPPS, A
• Format: Journal Article
• Language: English
• Published: Oxford Blackwell 01-06-1994
• Subjects: Adult; Base Sequence; Biological and medical sciences; Cell Adhesion Molecules - biosynthesis; Cell Adhesion Molecules - genetics; Cycloheximide - pharmacology; Cytokines - biosynthesis; Cytokines - genetics; DNA Primers - genetics; DNA Probes - genetics; Duodenum - cytology; Duodenum - immunology; Female; Fibroblasts - drug effects; Fibroblasts - immunology; Fundamental and applied biological sciences. Psychology; Gene Expression - drug effects; Granulocyte-Macrophage Colony-Stimulating Factor - biosynthesis; Granulocyte-Macrophage Colony-Stimulating Factor - genetics; Humans; In Vitro Techniques; Inflammation; Interleukin-1 - pharmacology; Interleukins - biosynthesis; Interleukins - genetics; Lipopolysaccharides - pharmacology; Middle Aged; Molecular and cellular biology; Molecular Sequence Data; Tumor Necrosis Factor-alpha - pharmacology; Human; Immunostimulation; Duodenum; Mucosa; Cytokine; Cell adhesion molecule; Inflammation; Gene expression; Gene; Interleukin 1; Lipopolysaccharide; Fibroblast; Tumor necrosis factor α
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.1994.tb06048.x

The role of mucosal fibroblasts in intestinal inflammatory reactions is not known. In this study, we demonstrate that fibroblasts grown from histologically normal human duodenal biopsy tissues expressed mRNA genes for granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-1 alpha, IL-1 beta, IL-6, IL-8, IL-10, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) when stimulated with lipopolysaccharide (LPS) or IL-1 alpha. The increased mRNA expression of GM-CSF, IL-1 alpha, IL-1 beta, IL-6 and IL-8 in response to IL-1 alpha and LPS stimulation was time- and dose-dependent. In contrast, IL-10 was weakly expressed when fibroblasts were stimulated with LPS, IL-1 alpha or tumour necrosis factor-alpha (TNF-alpha), but the expression was enhanced in the presence of cycloheximide combined with optimal concentrations of LPS, IL-1 alpha or TNF-alpha, IL-1 alpha was a more potent stimulator than LPS for GM-CSF, IL-6, IL-8 and IL-10 expression, but not for IL-1 alpha and IL-1 beta. Increased GM-CSF, IL-6 and IL-8 gene expression was associated with the production of cytokine proteins in culture supernatant, but IL-1 alpha and IL-1 beta remained undetectable. Dexamethasone suppressed both gene expression and protein production of GM-CSF, IL-6 and IL-8 when fibroblasts were exposed to IL-1 alpha. TNF-alpha stimulated the release of GM-CSF, IL-6 and IL-8 and, combined with IL-1 alpha, cytokine production was enhanced synergistically. Finally, both LPS and IL-1 alpha up-regulated ICAM-1 and VCAM-1 gene expression. These findings implicate duodenal fibroblasts in the initiation and/or regulation of intestinal inflammation.