Mechanism of IL-1beta-induced increase in intestinal epithelial tight junction permeability.
نویسندگان
چکیده
The IL-1beta-induced increase in intestinal epithelial tight junction (TJ) permeability has been postulated to be an important mechanism contributing to intestinal inflammation of Crohn's disease and other inflammatory conditions of the gut. The intracellular and molecular mechanisms that mediate the IL-1beta-induced increase in intestinal TJ permeability remain unclear. The purpose of this study was to elucidate the mechanisms that mediate the IL-1beta-induced increase in intestinal TJ permeability. Specifically, the role of myosin L chain kinase (MLCK) was investigated. IL-1beta caused a progressive increase in MLCK protein expression. The time course of IL-1beta-induced increase in MLCK level correlated linearly with increase in Caco-2 TJ permeability. Inhibition of the IL-1beta-induced increase in MLCK protein expression prevented the increase in Caco-2 TJ permeability. Inhibition of the IL-1beta-induced increase in MLCK activity also prevented the increase in Caco-2 TJ permeability. Additionally, knock-down of MLCK protein expression by small interference RNA prevented the IL-1beta-induced increase in Caco-2 TJ permeability. The IL-1beta-induced increase in MLCK protein expression was preceded by an increase in MLCK mRNA expression. The IL-1beta-induced increase in MLCK mRNA transcription and subsequent increase in MLCK protein expression and Caco-2 TJ permeability was mediated by activation of NF-kappaB. In conclusion, our data indicate that the IL-1beta increase in Caco-2 TJ permeability was mediated by an increase in MLCK expression and activity. Our findings also indicate that the IL-1beta-induced increase in MLCK protein expression and Caco-2 TJ permeability was mediated by an NF-kappaB-dependent increase in MLCK gene transcription.
منابع مشابه
Cellular and molecular mechanism of interleukin-1β modulation of Caco-2 intestinal epithelial tight junction barrier
Interleukin-1β (IL-1β) is a prototypical multifunctional cytokine that plays an important role in intestinal inflammation of Crohn's disease and other inflammatory conditions of the gut. Previous studies have shown that IL-1β causes an increase in intestinal epithelial tight junction (TJ) permeability both in in vivo animal and in vitro cell culture model systems. The IL-1β-induced increase in ...
متن کاملMechanism of cytokine modulation of epithelial tight junction barrier.
Cytokines play a crucial role in the modulation of inflammatory response in the gastrointestinal tract. Pro-inflammatory cytokines including tumor necrosis factor-alpha, interferon-gamma, interleukin-1beta?IL-1beta?, and interleukin-12 are essential in mediating the inflammatory response, while anti-inflammatory cytokines including interleukin-10 and transforming growth factor-beta are importan...
متن کاملSoluble uric acid induces inflammation via TLR4/NLRP3 pathway in intestinal epithelial cells
Objective(s): Hyperuricemia is a risk for cardiovascular and metabolic diseases, but the mechanism is ambiguous. Increased intestinal permeability is correlated with metabolic syndrome risk factors. Intestinal epithelial cells play a pivotal role in maintaining intestinal permeability. Uric acid is directly eliminated into intestinal lumen, however, the mechanism and e...
متن کاملTNF- -induced increase in intestinal epithelial tight junction permeability requires NF- B activation
Ma, Thomas Y., Gary K. Iwamoto, Neil T. Hoa, Vimesh Akotia, Ali Pedram, Michel A. Boivin, and Hamid M. Said. TNFinduced increase in intestinal epithelial tight junction permeability requires NFB activation. Am J Physiol Gastrointest Liver Physiol 286: G367–G376, 2004; 10.1152/ajpgi.00173.2003.—Crohn’s disease (CD) patients have an abnormal increase in intestinal epithelial permeability. The def...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Journal of immunology
دوره 180 8 شماره
صفحات -
تاریخ انتشار 2008