Differential Influence of Inositol Hexaphosphate on the Expression of Genes Encoding TGF-β Isoforms and Their Receptors in Intestinal Epithelial Cells Stimulated with Proinflammatory Agents
Transforming growth factor β (TGF-β) is a multifunctional cytokine recognized as an important regulator of inflammatory responses. The effect of inositol hexaphosphate (IP6), a naturally occurring phytochemical, on the mRNA expression of TGF-β1, TGF-β2, TGF-β3 and TβRI, TβRII, and TβRIII receptors stimulated with bacterial lipopolysaccharides (Escherichia coli and Salmonella typhimurium) and IL-1β in intestinal cells Caco-2 for 3 and 12？h was investigated. Real-time qRT-PCR was used to validate mRNAs level of examined genes. Bacterial endotoxin promoted differential expression of TGF-βs and their receptors in a time-dependent manner. IL-1β upregulated mRNA levels of all TGF-βs and receptors at both 3？h and 12？h. IP6 elicited the opposed to LPS effect by increasing downregulated transcription of the examined genes and suppressing the expression of TGF-β1 at 12？h. IP6 counteracted the stimulatory effect of IL-1β on TGF-β1 and receptors expression by decreasing their mRNA levels. IP6 enhanced LPS- and IL-1β-stimulated mRNA expression of TGF-β2 and -β3. Based on these studies it may be concluded that IP6 present in the intestinal milieu may exert immunoregulatory effects and chemopreventive activity on colonic epithelium under inflammatory conditions or during microbe-induced infection/inflammation by modulating the expression of genes encoding TGF-βs and their receptors at transcriptional level. 1. Introduction Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract thought to be a result of dysregulated or aberrant immune response to intestinal flora and multiple environmental factors with regard to genetic predisposition [1]. Exposure of intestinal epithelial cells (IEC) to bacterial components and products can potentially initiate intestinal inflammation by their release of cytokines chemokines and recruitment of inflammatory cells. IEC can also respond to a broad array of cytokines with altered gene expression and growth characteristics [2]. Cytokine that plays a crucial role in the inflammatory diseases such as IBD is IL-1 . Enhanced level of this cytokine has been determined in mucosal tissues infected with enteropathogenic bacteria, as well as in mucosal biopsies with active IBD. IL-1 activates intracellular signaling cascades in IEC leading to the increase of expression and secretion of proinflammatory cytokines and chemokines, uncontrolled intestinal inflammation, and disruption of epithelial function [3, 4]. Lipopolysaccharide (LPS) or endotoxin, the key component of the cell wall of Gram-negative bacteria,
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