Alterations in protein kinase C isoforms in experimentally-induced colitis in the rat

Chang, Qing; Soper, B. D.; Yacyshyn, Bruce; Tepperman, Barry L.

doi:10.1007/pl00000200

Cited by 11 publications

(5 citation statements)

References 44 publications

(50 reference statements)

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“…On the basis of these observations, activation of PKC-␣ by S. typhimurium SipA likely plays an important role in mediating proinflammatory responses, rather than altering tight junctional components. Indeed, our finding that rSipA induced the activation of PKC-␣, -␦, and -⑀ in intestinal epithelial cells but that only PKC-␣ appears to be involved in transepithelial signaling to PMN is consistent with recent studies that investigated the role of PKC isoforms in trinitrobenzene sulfonic acid-induced models of colitis in rats (1). Analogous to our findings, experimentally induced colitis in the rat resulted in elevated levels and activation of PKC-␣, -␦, and -⑀, and, in addition, these studies report that early expression and activation of PKC-␣ may play an important role in promoting colitis in this acute model of inflammation.…”

Section: Discussionsupporting

confidence: 92%

Salmonella typhimuriumSipA-induced neutrophil transepithelial migration: involvement of a PKC-α-dependent signal transduction pathway

Silva¹,

Song²,

Nadeau³

et al. 2004

American Journal of Physiology-Gastrointestinal and Liver Physi

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Salmonella typhimurium elicits an intense proinflammatory response characterized by movement of polymorphonuclear neutrophils (PMN) across the epithelial barrier to the intestinal lumen. We previously showed that S. typhimurium, via the type III secretion system effector protein SipA, initiates an ADP-ribosylation factor-6- and phospholipase D-dependent lipid-signaling cascade that directs activation of protein kinase C (PKC) and subsequent transepithelial movement of PMN. Here we sought to determine the specific PKC isoforms that are induced by the S. typhimurium effector SipA in model intestinal epithelia and to link the functional consequences of these isoforms in the promotion of PMN transepithelial migration. In vitro kinase PKC activation assays performed on polarized monolayers of T84 cells revealed that S. typhimurium and recombinant SipA induced activation of PKC-alpha, -delta, and -epsilon. To elucidate which of these isoforms play a key role in mediating epithelial cell responses that lead to the observed PMN transepithelial migration, we used a variety of PKC inhibitors with different isoform selectivity profiles. Inhibitors selective for PKC-alpha (Gö-6976 and 2,2',3,3',4,4'-hexahydroxyl-1,1'-biphenyl-6,6'-dimethanoldimethyl ether) markedly reduced S. typhimurium- and recombinant SipA-induced PMN transepithelial migration, whereas inhibitors to PKC-delta (rottlerin) or PKC-epsilon (V1-2) failed to exhibit a significant decrease in transepithelial movement of PMN. These results were confirmed biochemically and by immunofluorescence coupled to confocal microscopy. Our results are the first to show that the S. typhimurium effector protein SipA can activate multiple PKC isoforms, but only PKC-alpha is involved in the signal transduction cascade leading to PMN transepithelial migration.

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Section: Discussionsupporting

confidence: 92%

Salmonella typhimuriumSipA-induced neutrophil transepithelial migration: involvement of a PKC-α-dependent signal transduction pathway

Silva¹,

Song²,

Nadeau³

et al. 2004

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…We next examined the possibility that PKC activation is involved in regulating the pathway leading to PMN transepithelial migration. Since activation of PKC has been associated with inflammatory disease, as demonstrated in animal models as well as in response to enteric pathogens (Jacobson et al ., 1995; Chang et al ., 2000; Savkovic et al ., 2003), we first examined whether EAEC 042 induces translocation of this enzyme to the host cell membrane. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Enteroaggregative Escherichia coli promotes transepithelial migration of neutrophils through a conserved 12-lipoxygenase pathway

Boll

Struve

Sander

et al. 2011

Cellular Microbiology

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Summary Enteroaggregative Escherichia coli (EAEC) induces release of pro-inflammatory markers and disruption of intestinal epithelial barriers in vitro suggesting an inflammatory aspect to EAEC infection. However, the mechanisms underlying EAEC-induced mucosal inflammatory responses and the extent to which these events contribute to pathogenesis is not well characterized. Employing an established in vitro model we demonstrated that EAEC prototype strain 042 induces migration of polymorphonuclear neutrophils (PMNs) across polarized T84 cell monolayers. This event was mediated through a conserved host cell signaling cascade involving the 12/15-LOX pathway and led to apical secretion of an arachidonic acid-derived lipid PMN chemoattractant, guiding PMNs across the epithelia to the site of infection. Moreover, supporting the hypothesis that inflammatory responses may contribute to EAEC pathogenesis, we found that PMN transepithelial migration promoted enhanced attachment of EAEC 042 to T84 cells. These findings suggest that EAEC-induced PMN infiltration may favor colonization and thus pathogenesis of EAEC.

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“…Thus, altered PKC signalling could underlie the reduced K Ca 3.1 activity in the colon of mice treated with DSS (Brown et al. , 1999; Chang et al. , 2000).…”

Section: Discussionmentioning

confidence: 99%

Loss of Ca²⁺‐mediated ion transport during colitis correlates with reduced ion transport responses to a Ca²⁺‐activated K⁺ channel opener

Hirota

McKay

2009

British J Pharmacology

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Background and purpose: Epithelial surface hydration is critical for proper gut function. However, colonic tissues from individuals with inflammatory bowel disease or animals with colitis are hyporesponsive to Cl -secretagogues. The Cl -secretory responses to the muscarinic receptor agonist bethanechol are virtually absent in colons of mice with dextran sodium sulphate (DSS)-induced colitis. Our aim was to define the mechanism underlying this cholinergic hyporesponsiveness.

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Alterations in protein kinase C isoforms in experimentally-induced colitis in the rat

Cited by 11 publications

References 44 publications

Salmonella typhimuriumSipA-induced neutrophil transepithelial migration: involvement of a PKC-α-dependent signal transduction pathway

Salmonella typhimuriumSipA-induced neutrophil transepithelial migration: involvement of a PKC-α-dependent signal transduction pathway

Enteroaggregative Escherichia coli promotes transepithelial migration of neutrophils through a conserved 12-lipoxygenase pathway

Loss of Ca²⁺‐mediated ion transport during colitis correlates with reduced ion transport responses to a Ca²⁺‐activated K⁺ channel opener

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Alterations in protein kinase C isoforms in experimentally-induced colitis in the rat

Cited by 11 publications

References 44 publications

Salmonella typhimuriumSipA-induced neutrophil transepithelial migration: involvement of a PKC-α-dependent signal transduction pathway

Salmonella typhimuriumSipA-induced neutrophil transepithelial migration: involvement of a PKC-α-dependent signal transduction pathway

Enteroaggregative Escherichia coli promotes transepithelial migration of neutrophils through a conserved 12-lipoxygenase pathway

Loss of Ca2+‐mediated ion transport during colitis correlates with reduced ion transport responses to a Ca2+‐activated K+ channel opener

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Loss of Ca²⁺‐mediated ion transport during colitis correlates with reduced ion transport responses to a Ca²⁺‐activated K⁺ channel opener