Human Endotoxemia Activates p38 MAP Kinase and p42/44 MAP Kinase, But Not c-Jun N-terminal Kinase

Blink, Bernt van den; Branger, Judith; Weijer, Sebastiaan; Deventer, S. J. H. Van; Poll, Tom van der; Peppelenbosch, Maikel P.

doi:10.1007/bf03401965

Cited by 16 publications

(8 citation statements)

References 22 publications

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“…The p38 and p42 MAPK activation is transient (41,42). The activation dynamics of p38 and p42 could be such that the peak of their activation has passed already at the three-hour time point, which is in accordance with studies in human endotoxemia studies: after an early peak of activation for both p38 and p42, a reduced phosphorylation state occurred (43). To investigate the full activity dynamics of p38 and p42, in future studies, kinome analysis on earlier time points should be performed.…”

Section: R E S E a R C H A R T I C L E M O L M Esupporting

confidence: 76%

Kinase Activity Profiling of Gram-Negative Pneumonia

Hoogendijk

Diks

Peppelenbosch

et al. 2011

Mol Med

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Pneumonia is a severe disease with high morbidity and mortality. A major causative pathogen is the Gram-negative bacterium Klebsiella (K.) pneumoniae. Kinases play an integral role in the transduction of intracellular signaling cascades and regulate a diverse array of biological processes essential to immune cells. The current study explored signal transduction events during murine Gram-negative pneumonia using a systems biology approach. Kinase activity arrays enable the analysis of 1,024 consensus sequences of protein kinase substrates. Using a kinase activity array on whole lung lysates, cellular kinase activities were determined in a mouse model of K. pneumoniae pneumonia. Notable kinase activities also were validated with phospho-specific Western blots. On the basis of the profiling data, mitogen-activated protein kinase (MAPK) signaling via p42 mitogen-activated protein kinase (p42) and p38 mitogen-activated protein kinase (p38) and transforming growth factor β (TGFβ) activity were reduced during infection, whereas v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) (SRC) activity generally was enhanced. AKT signaling was represented in both metabolic and inflammatory (mitogen-activated protein kinase kinase 2 [MKK], apoptosis signal-regulating kinase/mitogen-activated protein kinase kinase kinase 5 [ASK] and v-raf murine sarcoma viral oncogene homolog B1 [b-RAF]) context. This study reaffirms the importance of classic inflammation pathways, such as MAPK and TGFβ signaling and reveals less known involvement of glycogen synthase kinase 3β (GSK-3β), AKT and SRC signaling cassettes in pneumonia.

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Section: R E S E a R C H A R T I C L E M O L M Esupporting

confidence: 76%

Kinase Activity Profiling of Gram-Negative Pneumonia

Hoogendijk

Diks

Peppelenbosch

et al. 2011

Mol Med

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“…Inflammatory mediators such as tumour necrosis factor (TNF) and interleukin-1 (IL-1) activate p38 MAPK, JNK and p42/44 MAPK [32,33]. Ikeda et al [34] also found evidence that cellular Ca 2+ acts as an upstream modulator of p38 MAPK.…”

Section: Discussionmentioning

confidence: 91%

Lipopolysaccharide Induces Inhibition of Galactose Intestinal Transport in Rabbits <i>in vitro</i>

Amador¹,

Marca

García-Herrera³

et al. 2008

Cell Physiol Biochem

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Background/Aims: Previous studies from our laboratory have revealed impaired intestinal absorption of D-galactose in lipopolysaccharide-treated rabbits. The aim of the present work was to examine the effect of LPS on D-galactose intestinal absorption in vitro. Methods: D-galactose intestinal transport was assessed employing three techniques: sugar uptake in rings of everted jejunum, transepithelial flux in Ussing-type chambers and transport assays in brush border membrane vesicles. The level of expression of the Na⁺/D-galactose cotransporter (SGLT1) was analyzed by Western blot. Results: LPS decreased the mucosal D-galactose transport in rabbit jejunum but a preexposition to the endotoxin was required. LPS affected the Na⁺-dependent transport system by increasing the apparent Km value without affecting the Vmax. It also decreased the Na⁺, K⁺-ATPase activity. However, it did not inhibit neither the uptake of D-galactose by brush border membrane vesicles nor modified the SGLT1 protein levels in the brush border, suggesting an indirect endotoxin effect. This inhibitory effect, was reduced by selective inhibitors of Ca²⁺-calmodulin (W13), protein kinase C (GF 109203X), p38 mitogen-activated protein kinase (SB 203580), c-Jun N-terminal kinase (SP 600125) and mitogen extracellular kinase (U 0126). Conclusion: LPS inhibits the mucosal Na⁺-dependent D-galactose intestinal absorption and the Na⁺, K⁺-ATPase activity when it is added to the tissue. Intracellular processes related to protein kinases seem to be implicated in the endotoxin effect.

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“…Signaling pathways necessary for systemic inflammation in humans are p38 MAPK and extracellular signal-regulated kinase (ERK) but not c-jun N-terminal kinase (JNK) [8]. In in vitro studies, blockade of p38 MAPK with SB203580 inhibited chemotactic movement of human neutrophils in a concentrationdependent manner [9] and prevented stimulus-induced formation of a leading edge in neutrophils by causing filamentous (F) actin to localize peripherally instead of in the lamellipod [10].…”

Section: Introductionmentioning

confidence: 99%