Novel Potentiation of Interleukin 1α Production in Endotoxin-Stimulated IC-21 Cells by Ambient Pressure Augmentation

Sawyer, Mark D.; Raaij, Tom van; Cross, J. C.; Sumpio, Bauer E.

doi:10.1001/archsurg.133.4.438

Cited by 4 publications

(6 citation statements)

References 7 publications

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“…IC-21 cells, derived from mouse peritoneal macrophages, exhibit many important features of macrophages including phagocytosis, 29 adherence, 25 and cytokine synthesis and secretion when stimulated with LPS. 24,25 WIF-B cells are hybrid cells from rat hepatoma and human fibroblast cells and feature in vitro many properties of hepatocytes as polarized cells in vivo, particularly sustainable rates of bile acid uptake over many days in culture. 18,30,31 These characteristics of the 2 cell lines make them suitable for studying cross talk between parenchymal and nonparenchymal liver cells in vitro.…”

Section: Discussionmentioning

confidence: 99%

“…24,25 Subsequent exposure of WIF-B cells to the IC-21 CM led to a substantial decrease of physiological transport function of bile acids across the basolateral membrane of WIF-B cells. A comparable effect could be achieved by exogenously adding recombinant cytokines to the WIF-B medium.…”

Section: Discussionmentioning

confidence: 99%

“…We chose to work with 2 cell lines, IC-21 and WIF-B cells, with their characteristics closely resembling the important functional properties of the related primary cells. IC-21 cells, derived from mouse peritoneal macrophages, exhibit many important features of macrophages including phagocytosis, 29 adherence, 25 and cytokine synthesis and secretion when stimulated with LPS. 24,25 WIF-B cells are hybrid cells from rat hepatoma and human fibroblast cells and feature in vitro many properties of hepatocytes as polarized cells in vivo, particularly sustainable rates of bile acid uptake over many days in culture.…”

Section: Discussionmentioning

confidence: 99%

“…Our findings on cytokine concentrations in IC-21 cell culture supernatant confirm the increased synthesis and secretion of inflammatory mediators in this cell line upon stimulation with LPS. 24,25 Subsequent exposure of WIF-B cells to the IC-21 CM led to a substantial decrease of physiological transport function of bile acids across the basolateral membrane of WIF-B cells. A comparable effect could be achieved by exogenously adding recombinant cytokines to the WIF-B medium.…”

Section: Discussionmentioning

confidence: 99%

“…The IC-21 macrophage line is derived from virally transformed mouse peritoneal macrophages and is an excellent model for in vitro studies of macrophage biology. 24,25 To determine the response of IC-21 macrophages to an endotoxin stimulus, the concentrations of the proinflammatory cytokines TNF-␣, IL-6, and IL-1␤ were determined in IC-21 cell culture medium after exposure to LPS for 24 hours. The concentrations of all 3 cytokines (TNF-␣, IL-6, and IL-1␤) were found to be markedly elevated in the supernatant of LPS-treated cells when compared with untreated controls (Fig.…”

Section: Quantitation Of Tnf-␣ Il-1␤mentioning

confidence: 99%

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Endotoxin-stimulated macrophages decrease bile acid uptake in WIF-B cells, a rat hepatoma hybrid cell line

Sturm

Zimmerman²,

Crawford³

et al. 2000

Hepatology

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In inflammatory disease states, such as hepatitis and sepsis, cholestasis is a common observation. 1,2 Although it is known that endotoxemia decreases hepatocellular bile acid uptake in vivo, the sequence of events leading to impairment of transport for bile salts is incompletely understood. The role of macrophages as mediators in endotoxemia or exposure of the liver to toxins such as alcohol or D-galactosamine, in particular through the release of proinflammatory cytokines, has been the focus of recent studies. [3][4][5] However, the question of whether macrophages are needed to mediate the cholestatic effect of inflammatory disease has not yet been clearly answered.Plasma membrane transport proteins for biliary solutes at both poles of the hepatocyte have been shown to be affected by endotoxin (lipopolysaccharide [LPS]). [6][7][8][9][10][11][12] On the canalicular membrane, mrp2, the organic anion transporter, is significantly down-regulated after LPS exposure. 8,11 In contrast, the canalicular bile acid transporter (bile salt export pump [BSEP]), is not substantively down-regulated during endotoxemia. 11 Several investigators have focused attention on the response of the sodium-taurocholate-cotransporting polypeptide (ntcp), the dominant transport protein for bile salts on the basolateral plasma membrane in a variety of inflammatory models. The effects of LPS or proinflammatory cytokines on ntcp have been the subject of intense investigation using in vivo models, 9,10,12 perfused rat liver, 6 hepatocyte cell culture, 13,14 and membrane preparations from the rat liver. 9,10 These studies show that ntcp protein expression and messenger RNA (mRNA) levels are down-regulated in the presence of LPS or proinflammatory cytokines. Recent studies provide evidence for hepatocellular alterations in regulatory nuclear transcription factors acting on the ntcp promoter 12 during endotoxemia. However, less information has been gained regarding extracellular mediators of endotoxin-induced cholestasis. It has been postulated but not proven that macrophages are responsible for the processing of LPS and the release of cytokines, which, in turn, adversely affect bile acid transport on the basolateral domain of the hepatocyte. 2 In this study, we show that LPS has a cholestatic effect on a hepatoma cell line only if macrophages are used as mediators. Tumor necrosis factor ␣ (TNF-␣), interleukin 1␤ (IL-1␤), and IL-6 were identified as effector cytokines causing diminished bile acid transport across the basolateral membrane and decreased expression of ntcp mRNA. Macrophage release of

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Quantitation Of Tnf-␣ Il-1␤mentioning

confidence: 99%

See 3 more Smart Citations

Endotoxin-stimulated macrophages decrease bile acid uptake in WIF-B cells, a rat hepatoma hybrid cell line

Sturm

Zimmerman²,

Crawford³

et al. 2000

Hepatology

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Effects of increased ambient pressure on colon cancer cell adhesion

Basson

Herden-Kirchoff

et al. 2000

J. Cell. Biochem.

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Forces such as strain modulate intestinal epithelial biology. Shear and pressure influence other cells. The effects of pressure on human colon cancer cells are poorly understood. Increasing ambient pressure for 30 min by 15 mm Hg over atmospheric stimulated adhesion to matrix proteins of four human colon cancer cell lines and primary cells from three human colon cancers, but not bovine aortic smooth-muscle cells. This effect was energy dependent and cation dependent (blocked by azide and chelation), accompanied by tyrosine phosphorylation of intracellular proteins including focal adhesion kinase, and blocked by tyrosine kinase inhibition (genistein, tyrphostin, and erbstatin) and a functional antibody to the beta1 integrin subunit. Although pressure stimulated adhesion even in a balanced salt solution, baseline and pressure-stimulated adhesion were each substantially diminished in the absence of serum. These data suggest that relatively low levels of increased pressure may stimulate malignant colonocyte adhesion by a cation-dependent beta1-integrin-mediated mechanism, perhaps via focal adhesion kinase-related tyrosine phosphorylation. In addition to elucidating another aspect of physical force regulation of colonocyte biology, these findings may be relevant to the effects of increased pressure engendered by colonic peristalsis, surgical manipulation, or laparoscopic surgery on colon cancer cell adhesion.

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Causes and consequences of cholestasis

Sturm¹

2004

KIND

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Een belangrijke functie van de lever is de vorming van gal. Bij patie¨nten met cholestase is de galvorming verstoord. Dit kan ontstaan door infecties, bepaalde geneesmiddelen of door een auto-immuunof stofwisselingsziekte. In dit proefschrift word onderzocht wat er op cellulair niveau gebeurt bij cholestase, in het bijzonder bij cholestase die ontstaat door sepsis. Doelstelling van het onderzoek was aan te tonen hoe de levercel zich aanpast aan de afwijkende galvorming en welke bijdrage de niet-parenchymale Kupffer-cellen hebben in de etiologie van cholestase.Voor een goede galvorming zijn de transportsystemen in hepatocyten van groot belang, met name het transport van galzouten vanuit het bloed naar de gal. Wanneer dit gestoord is, zoals bij cholestase, dan hopen galzouten zich op in de levercellen en in plasma. Bij sepsis spelen Kupffer-cellen een rol. Wanneer deze cellen in contact komen met lipopolysachariden, stoffen uit celwanden van gramnegatieve bacterie¨n, worden zij geactiveerd en er ontstaat een acutefasereactie in de lever. Kupffer-cellen scheiden dan eiwitten (cytokinen en chemokinen) en andere mediatoren (platelet-activating factor, reactieve zuurstofspecies) uit die zorgen voor een ontstekingsreactie om de infectie tegen te gaan. De cytokinen blijken verantwoordelijk te zijn voor het remmen van belangrijke transportfuncties in de levercel. Deze processen leiden tot cholestase. Echter, de hepatocyttransportfunctie voor galzuren blijft intact wanneer de effecten van de cytokinen worden geneutraliseerd of wanneer de Kupffer-cellen worden geı¨nactiveerd. Dit is een resultaat in dierexperimenteel onderzoek en in een laboratoriumstudie met cellijnen. Dus kunnen de Kupffer-cellen bij de ontwikkeling van medicijnen ter preventie of behandeling van cholestase een belangrijk doelwit zijn.Bij cholestase hopen galzouten zich op in verschillende delen van de levercel. Om zich te beschermen, beschikken levercellen over verschillende aanpassingsmechanismen, o.a. nucleaire receptoren. Nucleaire receptoren zijn eiwitten die door bepaalde liganden kunnen worden geactiveerd en daardoor de expressie van belangrijke genen in cellen kunnen reguleren. Een van de nucleaire receptoren die in de lever tot expressie komt, heeft een functie als een intracellulaire sensor voor galzouten (de Farnesoid-xreceptor of FXR). FXR kan na activatie door binding van galzouten belangrijke genen voor synthese en transport van galzouten reguleren. Onder andere is door activatie van een tweede nucleaire receptor (small heterodimer partner, SHP) ook een remming van galzoutopname in de hepatocyt mogelijk. Door onderzoek in getransfecteerde cellijnen bleek deze laatste regulatie, die ter preventie van een ophoping van schadelijke galzouten in de levercel aanwezig is, zeer effectief te zijn. Verder is er een koppeling van lipiden-en galzoutmetabolisme via FXR. FXR is in staat de expressie van apolipoproteı¨ne-A-I te remmen, die bij de aanmaak van high-density lipoproteı¨-nen belangrijk is. Nucleaire receptoren kunnen dus een rol spelen in de et...

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Novel Potentiation of Interleukin 1α Production in Endotoxin-Stimulated IC-21 Cells by Ambient Pressure Augmentation

Cited by 4 publications

References 7 publications

Endotoxin-stimulated macrophages decrease bile acid uptake in WIF-B cells, a rat hepatoma hybrid cell line

Endotoxin-stimulated macrophages decrease bile acid uptake in WIF-B cells, a rat hepatoma hybrid cell line

Effects of increased ambient pressure on colon cancer cell adhesion

Causes and consequences of cholestasis

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