Reactive oxygen intermediates and eicosanoid production by Kupffer cells and infiltrated macrophages in acute and chronic liver injury induced in rats by CCl 4

Alric, Laurent; Orfila, C; Carrère, Nicolas; Béraud, Maryse; Carrera, G.; Lepert, Jean-Claude; Duffaut, M; Pipy, Bernard; Vinel, Jean Pierre

doi:10.1007/s000110050649

Cited by 50 publications

(41 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Acute hepatic injury is caused by CCl 4 -induced formation of a highly reactive carbon-entered trichloromethyl radical through cytochrom-P450 isoenzymes that interacts with hepatic proteins as well as lipids and deteriorates cellular membrane [38]. CCl 4 exposure upregulates the expression of many cytokine genes, including IL-1β, IL-6, TGF-β, and synthesis of reactive oxygen species [38,39]. In the current study, we demonstrated, for the first time, that secreted IL-1α, but not membrane IL-1α, aggravated CCl 4 -induced liver injury (Fig.…”

Section: Discussionmentioning

confidence: 99%

Secreted IL‐1α promotes T‐cell activation and expansion of CD11b⁺Gr1⁺ cells in carbon tetrachloride‐induced liver injury in mice

et al. 2015

View full text Add to dashboard Cite

Interleukin-1α is mainly expressed on the cell membrane, but can also be secreted during inflammation. The roles of secreted and membrane IL-1α in acute liver inflammation are still not known. Here, we examined the functions of secreted and membrane IL-1α in a mouse model of carbon tetrachloride-induced acute liver injury. We show that secreted IL-1α aggravates liver damage and membrane IL-1α slightly protects mice from liver injury. Further studies showed that secreted IL-1α promotes T-cell activation. It also increased the expansion of CD11b + Gr1 + myeloid cells, which may serve as a negative regulator of acute liver inflammation. Moreover, secreted IL-1α induced IL-6 production from hepatocytes. IL-6 neutralization reduced the proliferation of CD11b + Gr1 + myeloid cells in vivo. CCL2 and CXCL5 expression was increased by secreted IL-1α in vitro and in vivo. Antagonists of the chemokine receptors for CCL2 and CXCL5 significantly reduced the migration of CD11b + Gr1 + myeloid cells. These results demonstrate that secreted and membrane IL-1α play different roles in acute liver injury. Secreted IL-1α could promote Tcell activation and the recruitment and expansion of CD11b + Gr1 + myeloid cells through induction of CCL2, CXCL5, and IL-6. The controlled release of IL-1α could be a critical regulator during acute liver inflammation.Keywords: Acute liver injury r CD11b + Gr1 + myeloid cells r Membrane IL-1α r Secreted IL-1α r T-cell activation Additional supporting information may be found in the online version of this article at the publisher's web-site Correspondence: Dr. Haiyan Liu e-mail: hliu@suda.edu.cn IntroductionThe liver plays a central role in metabolic homeostasis [1]. Liver injury is mainly caused by various insults such as drug, chemical agents, viral hepatitis (hepatitis B or C viruses), alcohol, and C 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2015. 45: 2084-2098 Molecular immunology 2085 autoimmune attack of hepatocytes [2]. Liver damage by proinflammatory cytokines induced by these causes is a relevant mechanism for liver cell death [3]. Acute liver injury remains one of the most challenging problems in liver diseases, and new therapeutic options for treatment of acute liver injury are urgently needed [4]. Carbon tetrachloride (CCl 4 ) is widely used as a chemical inducer of acute or chronic liver injury in rodents depending on the dosage and administration frequency [5]. ROS and oxidative stress are then generated and inflammatory cells are recruited, which leads to hepatocyte degeneration and necrosis [6,7]. Parenchymal cells could regenerate that involves a complex regulated response after CCl 4 -induced acute liver injury [8]. Therefore, anti-oxidative and anti-inflammatory therapies are thought to be the effective ways to prevent and attenuate CCl 4 -induced liver damage. IL-1 is a pleiotropic cytokine and affects inflammatory immune responses. The IL-1 family includes two important agonistic proteins, IL-1α and IL-1β, which play an important role in ...

show abstract

Section: Discussionmentioning

confidence: 99%

Secreted IL‐1α promotes T‐cell activation and expansion of CD11b⁺Gr1⁺ cells in carbon tetrachloride‐induced liver injury in mice

et al. 2015

View full text Add to dashboard Cite

show abstract

“…21 In addition, the isolated Kupffer cells from livers with steatonecrosis and CCl 4 cirrhosis present an imbalance in COX metabolites with an overproduction of TXA 2 and a decrease of PGE 2 . 22 It is therefore possible that the binding of different vasoconstrictors to G-protein-coupled receptors increases the release of arachidonic acid and results in an increased production of vasoconstrictive prostanoids, contracting the hepatic vascular bed and contributing to the observed increase in hepatic vascular resistance of cirrhotic livers.…”

mentioning

confidence: 99%

Cyclooxygenase-derived products modulate the increased intrahepatic resistance of cirrhotic rat livers

et al. 2003

View full text Add to dashboard Cite

In cirrhotic livers, increased resistance to portal flow, in part due to an exaggerated response to vasoconstrictors, is the primary factor in the pathophysiology of portal hypertension. Our aim was to evaluate the response of the intrahepatic circulation of cirrhotic rat livers to the I n cirrhotic livers, increased resistance to portal blood flow is the primary factor in the pathophysiology of portal hypertension. 1 This increased resistance is determined in part by the architectural distortion of the hepatic structure caused by cirrhosis. However, substantial evidence shows that a dynamic component, caused by the active contraction of vascular and extravascular contractile cells, plays a major role in further increasing intrahepatic resistance. 2 This dynamic component of hepatic vascular resistance is believed to be the consequence of an imbalance between the vasodilator/vasoconstrictor forces that regulate hepatic vascular tone. 1 In addition, the hepatic vascular resistance of cirrhotic livers exhibits a hyperresponse to several vasoconstrictors, such as endothelin 1, 3 norepinephrine, 4 or leukotriene D 4 . 5 Nitric oxide blunts the response of the hepatic vascular bed to several vasoconstrictors, 6 and its production is decreased in the cirrhotic liver. It is therefore possible that an insufficient availability of NO 7 could account for the hyperresponse to vasoconstrictors observed in cirrhotic livers.In addition, it has been shown that the activation of G protein-coupled receptors, such as those for ␣ 1 -adrenergic agonists, vasopressin, or endothelin 1, stimulates release of arachidonic acid, leading to the formation of its vasoactive-derived metabolites, including prostaglandins (PGs), thromboxanes (TXs), and leukotrienes. [8][9][10] Cyclooxygenase (COX)

show abstract

“…The elevated production of eicosanoids is normally associated with upregulation of key enzymes such as COX in the biosynthesis pathway. A recent study by Alric et al (1) showed a significant release of thromboxane B 2 (TXB 2 ), a stable metabolite of TXA 2 , from isolated Kupffer cells of the CCl 4 -induced cirrhotic rat liver. Another study by Nanji et al (25) found increased mRNA levels of COX-2, the inducible form of the COX enzyme, in rat liver samples of CCl 4 -induced cirrhosis, suggesting an upregulation of COX-2 enzyme.…”

mentioning

confidence: 99%

Role of thromboxane A₂in early BDL-induced portal hypertension

Yokoyama

Kresge

et al. 2003

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

Although the mechanisms of cirrhosis-induced portal hypertension have been studied extensively, the role of thromboxane A2 (TXA2) in the development of portal hypertension has never been explicitly explored. In the present study, we sought to determine the role of TXA2 in bile duct ligation (BDL)-induced portal hypertension in Sprague-Dawley rats. After 1 wk of BDL or sham operation, the liver was isolated and perfused with Krebs-Henseleit bicarbonate buffer at a constant flow rate. After 30 min of nonrecirculating perfusion, the buffer was recirculated in a total volume of 100 ml. The perfusate was sampled for the enzyme immunoassay of thromboxane B2(TXB2), the stable metabolite of TXA2. Although recirculation of the buffer caused no significant change in sham-operated rats, it resulted in a marked increase in portal pressure in BDL rats. The increase in portal pressure was found concomitantly with a significant increase of TXB2 in the perfusate (sham vs. BDL after 30 min of recirculating perfusion: 1,420 ± 803 vs. 10,210 ± 2,950 pg/ml; P < 0.05). Perfusion with a buffer containing indomethacin or gadolinium chloride for inhibition of cyclooxygenase (COX) or Kupffer cells, respectively, substantially blocked the recirculation-induced increases in both portal pressure and TXB2 release in BDL group. Hepatic detection of COX gene expression by RT-PCR revealed that COX-2 but not COX-1 was upregulated following BDL, and this upregulation was confirmed at the protein level by Western blot analysis. In conclusion, these results clearly demonstrate that increased hepatic TXA2 release into the portal circulation contributes to the increased portal resistance in BDL-induced liver injury, suggesting a role of TXA2 in liver fibrosis-induced portal hypertension. Furthermore, the Kupffer cell is likely the source of increased TXA2, which is associated with upregulation of the COX-2 enzyme.

show abstract

Reactive oxygen intermediates and eicosanoid production by Kupffer cells and infiltrated macrophages in acute and chronic liver injury induced in rats by CCl 4

Cited by 50 publications

References 41 publications

Secreted IL‐1α promotes T‐cell activation and expansion of CD11b⁺Gr1⁺ cells in carbon tetrachloride‐induced liver injury in mice

Secreted IL‐1α promotes T‐cell activation and expansion of CD11b⁺Gr1⁺ cells in carbon tetrachloride‐induced liver injury in mice

Cyclooxygenase-derived products modulate the increased intrahepatic resistance of cirrhotic rat livers

Role of thromboxane A₂in early BDL-induced portal hypertension

Contact Info

Product

Resources

About

Reactive oxygen intermediates and eicosanoid production by Kupffer cells and infiltrated macrophages in acute and chronic liver injury induced in rats by CCl 4

Cited by 50 publications

References 41 publications

Secreted IL‐1α promotes T‐cell activation and expansion of CD11b+Gr1+ cells in carbon tetrachloride‐induced liver injury in mice

Secreted IL‐1α promotes T‐cell activation and expansion of CD11b+Gr1+ cells in carbon tetrachloride‐induced liver injury in mice

Cyclooxygenase-derived products modulate the increased intrahepatic resistance of cirrhotic rat livers

Role of thromboxane A2in early BDL-induced portal hypertension

Contact Info

Product

Resources

About

Secreted IL‐1α promotes T‐cell activation and expansion of CD11b⁺Gr1⁺ cells in carbon tetrachloride‐induced liver injury in mice

Secreted IL‐1α promotes T‐cell activation and expansion of CD11b⁺Gr1⁺ cells in carbon tetrachloride‐induced liver injury in mice

Role of thromboxane A₂in early BDL-induced portal hypertension