IL-6 is an inflammatory cytokine known to be elevated in chronic diseases and following insults such as trauma and infection. While necessary for the development of B cells and Th17 cells, IL-6, at elevated levels, can also cause tissue damage and lead to a rise in inflammation. Previous work in our laboratory has shown that IL-6 is increased both systemically as well as in multiple organ systems including the ileum following ethanol exposure and burn injury. As this combined insult causes elevated intestinal morphological damage, tight junction protein localization alterations, and phospho myosin light chain (pMLC) levels, we sought to determine the role of IL-6 in these intestinal responses using a model of binge ethanol exposure and burn injury. IL-6 antibody treatment after the combined insult reduced morphological changes in the ileum, bacterial translocation, and pMLC levels relative to either injury alone. ZO-1 and occludin localization was also re-established in wild type mice given IL-6 antibody after ethanol and burn. IL-6 knockout mice given ethanol and burn injury also had reduced intestinal damage; however, no changes in bacterial translocation or tight junction protein localization were observed as compared to similarly treated wild type mice. These data suggest that IL-6 may have a role in intestinal tissue damage observed following the combined insult of binge ethanol exposure and burn injury although complete loss of IL-6 does not appear to be beneficial in this model. Modulation of IL-6 may present a new option for preventing intestinal damage and associated inflammation following a combined insult of ethanol exposure and burn injury.
Epithelial tight junctions are critical for creating a barrier yet allowing paracellular transport. Although it is well established that the actin cytoskeleton is critical for preserving the dynamic organization of the tight junction and maintaining normal tight junction protein recycling, contributions of microtubules to tight junction organization and function remain undefined. The aim of this study is to determine the role of microtubules in tight junction homeostasis and restoration. Our data demonstrate that occludin traffics on microtubules and that microtubule disruption perturbs tight junction structure and function. Microtubules are also shown to be required for restoring barrier function following Ca(2+) chelation and repletion. These processes are mediated by proteins participating in microtubule minus-end-directed trafficking but not plus-end-directed trafficking. These studies show that microtubules participate in the preservation of epithelial tight junction structure and function and play a vital role in tight junction restoration, thus expanding our understanding of the regulation of tight junction physiology.
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