Title: The role of the Rho-associated kinase ROCK in the differential regulation of CXCL8 and CCL2 production by Caco-2 epithelial cells. (120.23)
Abstract: Abstract Two chemokines found at elevated levels in Inflammatory Bowel Disease (IBD), CXCL8 and CCL2, may play important roles in perpetuating the chronic inflammation that characterizes this condition. Interleukin-1 (IL-1) and Tumor Necrosis Factor-α (TNF-α), which have both been found at elevated levels in IBD, can stimulate the production of CXCL8 and CCL2 by Caco-2 epithelial cells. Previous results from our laboratory have shown that ROCK may be essential for optimal production of CXCL8, as suppression of ROCK activity with Y27632 suppressed IL-1 induced CXCL8 production. We now show that inhibiting ROCK also suppresses TNF-α induced CXCL8 mRNA and protein secretion similar to previously seen with IL-1. Furthermore, inhibiting ROCK suppressed TNF-induced phosphorylation of JNK, but had no effect on IκBα phosphorylation or degradation. Yet inhibition of ROCK actually resulted in significantly elevated levels of CCL2 mRNA with IL-1 and TNF stimulation, and TNF-induced CCL2 secretion was significantly increased while IL-1-induced CCL2 secretion was unchanged. These results suggest that ROCK does play a role in regulating chemokine production in intestinal epithelial cells, but in a very different manner for CXCL8 compared to CCL2. While the purpose of this differential regulation is unclear, it may be an important mechanism for modulating the influx of specific groups of inflammatory cells into affected tissues.
Publication Year: 2012
Publication Date: 2012-05-01
Language: en
Type: article
Indexed In: ['crossref']
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Cited By Count: 2
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