Increased expression of interleukin-8 mRNA in ulcerative colitis and Crohn's disease mucosa and epithelial cells

Abstract

: Interleukin-8 (IL-8) is a chemotactic cytokine (chemokine), which both attracts and activates granulocytes. IL-8 could have a central function in the initiation and perpetuation of the inflammatory bowel diseases (IBD), due to its relative resistance to inactivation and long half-life in vivo. Using a quantitative reverse transcriptase polymerase chain reaction (RT-PCR) assay, we have observed elevated levels of IL-8 mRNA in colonic mucosal sections obtained from surgically resected specimens from ulcerative colitis (UC) and Crohn's disease (CD) patients with actively inflamed mucosa. The level of IL-8 mRNA expression in the intestinal mucosal biopsies from UC and CD patients was much greater in involved as opposed to noninvolved mucosal sections. The highest expression of IL-8 mRNA detected by RT-PCR was in UC mucosa and in isolated intestinal epithelial cells from UC patients. Increased IL-8 production by cells in IBD intestinal mucosa as well as IBD epithelial cells may be involved in the continuous attraction and activation of granulocytes in the inflamed intestine in both UC and CD patients. Chemokines, such as IL-8, are potent chemoattractant molecules and may have a central role in the augmentation and perpetuation of inflammation in IBD.

Intestinal Interleukin-8 Concentration and Gene Expression in Inflammatory Bowel Disease

“…In the present study detectable mRNA IL-8 levels were found even in mucosal specimens from patients with inactive IBD but not in non-inflammatory IBS disease-specific controls when using a quantitative PCR technique, indicating that gene expression is increased even in IBD bowel segments without macroscopic inflammation. The pattern of localization of IL-8 mRNA may differ in UC and CD, as the gene expression was more pronounced in active CD, which is in contradiction to previously published results (7,28,29). However, all 30 IBD patients in one of these papers (7) were receiving glucocorticoid therapy when tissue samples were obtained, which, as mentioned earlier, affects IL-8 expression and production and thus may explain this discrepancy.…”

The CD40-CD40L Pathway Contributes to the Proinflammatory Function of Intestinal Epithelial Cells in Inflammatory Bowel Disease

“…42 Expression levels in affected tissue were much higher as opposed to noninvolved adjacent mucosa, which is similar to our findings regarding the epithelial CD40 expression. A similar correlation was observed for the IL-8 production in IECs, which is in line with our immunofluorescence results depicting epithelial IL-8 staining in active CD and UC in contrast to noninflamed tissue.…”

Interleukin-8 stimulates the migration of human colonic epithelial cells in vitro

“…This is likely also to apply in LIM1215 cells, since trichostatin A, a more potent inhibitor of histone deacetylase than butyrate, exerted greater effects on IL-8 secretion than an optimal butyrate concentration. As reported previously in other colon cancer cell lines [11,13], both PMA and TNF-α increased IL-8 secretion.…”

“…It is secreted constitutively by isolated colonic crypts and colon cancer cell lines [11,12], and a range of factors, such as SCFAs, PMA, IL-1 and tumour necrosis factor-α (TNF-α), are known to upregulate this secretion [11][12][13][14][15]. Despite this, the influence of IL-8 on colonic epithelial migration has not been established.…”