Tauroursodeoxycholic acid enhances phagocytosis of the cultured rat Kupffer cell

Funaoka, Masato; Komatsu, Masafumi; Toyoshima, Itaru; Mikami, Koji; Ono, Tsuyoshi; Hoshino, Takao; Kato, Junji; Kuramitsu, Tomoyuki; Ishii, Tatsuya; Masamune, Osamu

doi:10.1046/j.1440-1746.1999.01931.x

Cited by 14 publications

(5 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, trimethylamine oxide and tauroursodeoxycholic acid were shown to stimulate phagocytosis by macrophages or Kupffer cells. 121,122 4-phenylbutyrate (also a deacetylase inhibitor) can rescue cells of various types from ER stress-induced apoptosis. 123,124 Two chaperones (tauroursodeoxycholic acid and 4-phenylbutyrate) are used in the treatment of other disorders.…”

Section: Discussionmentioning

confidence: 99%

The Macrophage at the Crossroads of Insulin Resistance and Atherosclerosis

Liang

Han

Senokuchi

et al. 2007

Circulation Research

123

105

View full text Add to dashboard Cite

Abstract-The macrophage has emerged as an important player in the pathogenesis of both atherosclerosis and insulin resistance. Cross-talk between inflammatory macrophages and adipocytes may be involved in insulin resistance in peripheral tissues. Defective insulin signaling in cells of the arterial wall including macrophages may promote the development of atherosclerosis. Insulin resistant macrophages are more susceptible to endoplasmic reticulum stress and apoptosis in response to various stimuli such as nutrient deprivation, free cholesterol loading, and oxidized LDL.

show abstract

Section: Discussionmentioning

confidence: 99%

The Macrophage at the Crossroads of Insulin Resistance and Atherosclerosis

Liang

Han

Senokuchi

et al. 2007

Circulation Research

123

105

View full text Add to dashboard Cite

show abstract

“…Macrophages phagocytic activity as well as cytokine production can be modulated by bile acids (Calmus et al 1992; Funaoka et al 1999; Minter et al 2005; Scott-Conner and Grogan 1994; Sung and Go 1999; Graf and Bode 2012). The influence of bile acids on the immune response has been reviewed recently (Fiorucci et al 2010; Graf and Bode 2012).…”

Section: Structure and Cellular Components Of The Livermentioning

confidence: 99%

Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME

Hewitt²,

et al. 2013

View full text Add to dashboard Cite

This review encompasses the most important advances in liver functions and hepatotoxicity and analyzes which mechanisms can be studied in vitro. In a complex architecture of nested, zonated lobules, the liver consists of approximately 80 % hepatocytes and 20 % non-parenchymal cells, the latter being involved in a secondary phase that may dramatically aggravate the initial damage. Hepatotoxicity, as well as hepatic metabolism, is controlled by a set of nuclear receptors (including PXR, CAR, HNF-4α, FXR, LXR, SHP, VDR and PPAR) and signaling pathways. When isolating liver cells, some pathways are activated, e.g., the RAS/MEK/ERK pathway, whereas others are silenced (e.g. HNF-4α), resulting in up- and downregulation of hundreds of genes. An understanding of these changes is crucial for a correct interpretation of in vitro data. The possibilities and limitations of the most useful liver in vitro systems are summarized, including three-dimensional culture techniques, co-cultures with non-parenchymal cells, hepatospheres, precision cut liver slices and the isolated perfused liver. Also discussed is how closely hepatoma, stem cell and iPS cell–derived hepatocyte-like-cells resemble real hepatocytes. Finally, a summary is given of the state of the art of liver in vitro and mathematical modeling systems that are currently used in the pharmaceutical industry with an emphasis on drug metabolism, prediction of clearance, drug interaction, transporter studies and hepatotoxicity. One key message is that despite our enthusiasm for in vitro systems, we must never lose sight of the in vivo situation. Although hepatocytes have been isolated for decades, the hunt for relevant alternative systems has only just begun.Electronic supplementary materialThe online version of this article (doi:10.1007/s00204-013-1078-5) contains supplementary material, which is available to authorized users.

show abstract

“…Hence, bile acids affect intracellular signaling in response to type I IFNs or cytokines, such as IL-6, and subsequent gene expression in immune cells, such as NK cells or lymphocytes, as well as in epithelial cells, such as hepatocytes [11][12][13][14][15]. Moreover, bile acids alter the primary humoral response in human monocytes by inhibition of cell proliferation and exocytosis of Ig [16], and a variety of different reports indicates that they substantially impair macrophage functions, including phagocytic activity, as well as production of the cytokines TNF-␣ or IL-6, in response to inflammatory stimuli, such as LPS [17][18][19][20]. Thereby, the inhibitory effects of bile acids on LPS-induced cytokine expression in different types of macro-phages, including alveolar macrophages, murine macrophages, and Kupffer cells, have been attributed largely to the activation of the G-protein-coupled bile acid receptor TGR5 and have been suggested to involve increased production of cAMP [18,21] and impaired activation of NF-B [22].…”

Section: Introductionmentioning

confidence: 99%

Bile acids PKA-dependently induce a switch of the IL-10/IL-12 ratio and reduce proinflammatory capability of human macrophages

Haselow

Bode

Wammers

et al. 2013

Journal of Leukocyte Biology

125

109

View full text Add to dashboard Cite

That cholestatic conditions are accompanied by an enhanced susceptibility to bacterial infection in human and animal models is a known phenomenon. This correlates with the observation that bile acids have suppressive effects on cells of innate and adaptive immunity. The present study provides evidence that in human macrophages, bile acids inhibit the LPS-induced expression of proinflammatory cytokines without affecting the expression of the anti-inflammatory cytokine IL-10. This results in a macrophage phenotype that is characterized by an increased IL-10/IL-12 ratio. Correspondingly, bile acids suppress basal phagocytic activity of human macrophages. These effects of bile acids can be mimicked by cAMP, which is presumably induced TGR5-dependently. The data provided further suggest that in primary human macrophages, modulation of the macrophage response toward LPS by bile acids involves activation of CREB, disturbed nuclear translocation of NF-κB, and PKA-dependent enhancement of LPS-induced cFos expression. The increase in cFos expression is paralleled by an enhanced formation of a protein complex comprising cFos and the p65 subunit of NF-κB. In summary, the data provided suggest that in human macrophages, bile acids induce an anti-inflammatory phenotype characterized by an increased IL-10/IL-12 ratio via activation of PKA and thereby, prevent their activation as classically activated macrophages. This bile acid-induced modulation of macrophage function may also be responsible for the experimentally and clinically observed anti-inflammatory and immunosuppressive effects of bile acids.

show abstract

Tauroursodeoxycholic acid enhances phagocytosis of the cultured rat Kupffer cell

Abstract: These observations suggest that tauroursodeoxycholic acid enhances membrane trafficking without changing translocation speed.

Cited by 14 publications

References 28 publications

The Macrophage at the Crossroads of Insulin Resistance and Atherosclerosis

The Macrophage at the Crossroads of Insulin Resistance and Atherosclerosis

Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME

Bile acids PKA-dependently induce a switch of the IL-10/IL-12 ratio and reduce proinflammatory capability of human macrophages

Contact Info

Product

Resources

About