Modulation of KC/gro Protein (Interleukin-8 Related Protein in Rodents) Release from Hepatocytes by Biologically-Active Mediators

Shiratori, Yasushi; Hikiba, Yohko; Mawet, E; Niwa, Yuki; Matsumura, Masaru; Kato, Natsumi; Shiina, S.; Tada, Mitsuhiro; Komatsu, Yutaka; Kawabe, Takao; Yoshida, Haruhiko; Okano, Kenichi; Omata, Masao

doi:10.1006/bbrc.1994.2340

Cited by 25 publications

(19 citation statements)

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“…Furthermore, some of these chemokines can also enhance endothelial cell proliferation (40). Because TNF-α can induce the expression of these chemokines in vitro and in vivo (23,24), the TNF-α/TNF receptor axis may regulate the angiogenic switch directly or indirectly by inducing the expression of chemokines, which can induce both the proliferation of endothelial cells and the infiltration of inflammatory cells, another rich source of angiogenic factors.…”

Section: Discussionmentioning

confidence: 99%

“…In AOM and DSS-treated TNF-Rp55 -/-mice, infiltration by both neutrophils and macrophages was markedly decreased, whereas lymphocyte and dendritic cell infiltration was minimally affected (Figure 2, C-G). TNF-α can augment the expression of the chemokines keratinocyte chemoattractant/CXCL1 (KC/CXCL1) and monocyte chemoattractant protein-1/CCL2 (MCP-1/CCL2), which are chemotactic for neutrophils and macrophages, respectively (23,24). Indeed, after day 7, gene expression of both chemokines was enhanced in WT mice, but their expression was consistently depressed in TNF-Rp55 -/-mice ( Figure 3).…”

Section: Inflammatory Cell Infiltrationmentioning

confidence: 99%

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Blocking TNF-α in mice reduces colorectal carcinogenesis associated with chronic colitis

Popivanova¹,

Kitamura²,

Wu³

et al. 2008

J. Clin. Invest.

616

661

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The inflammatory bowel disease ulcerative colitis (UC) frequently progresses to colon cancer. To understand the mechanisms by which UC patients develop colon carcinomas, we used a mouse model of the disease whereby administration of azoxymethane (AOM) followed by repeated dextran sulfate sodium (DSS) ingestion causes severe colonic inflammation and the subsequent development of multiple tumors. We found that treating WT mice with AOM and DSS increased TNF-α expression and the number of infiltrating leukocytes expressing its major receptor, p55 (TNF-Rp55), in the lamina propria and submucosal regions of the colon. This was followed by the development of multiple colonic tumors. Mice lacking TNF-Rp55 and treated with AOM and DSS showed reduced mucosal damage, reduced infiltration of macrophages and neutrophils, and attenuated subsequent tumor formation. WT mice transplanted with TNF-Rp55-deficient bone marrow also developed significantly fewer tumors after AOM and DSS treatment than either WT mice or TNF-Rp55-deficient mice transplanted with WT bone marrow. Furthermore, administration of etanercept, a specific antagonist of TNF-α, to WT mice after treatment with AOM and DSS markedly reduced the number and size of tumors and reduced colonic infiltration by neutrophils and macrophages. These observations identify TNF-α as a crucial mediator of the initiation and progression of colitis-associated colon carcinogenesis and suggest that targeting TNF-α may be useful in treating colon cancer in individuals with UC.

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Section: Discussionmentioning

confidence: 99%

Section: Inflammatory Cell Infiltrationmentioning

confidence: 99%

Blocking TNF-α in mice reduces colorectal carcinogenesis associated with chronic colitis

Popivanova¹,

Kitamura²,

Wu³

et al. 2008

J. Clin. Invest.

616

661

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“…The relatively small fold change for most genes can be explained by the time point chosen (8 h). Data from many pervious studies indicate that LPS can stimulate hepatocytes directly, in the absence of cytokines, to modulate various products of hepatocytes (1,13,22,24,37,42,43,47,48,50,51,58).…”

Section: Discussionmentioning

confidence: 99%

Role of Toll-Like Receptors in Changes in Gene Expression and NF-κB Activation in Mouse Hepatocytes Stimulated with Lipopolysaccharide

et al. 2002

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The liver is an important site of host-microbe interaction. Although hepatocytes have been reported to be responsive to lipopolysaccharide (LPS), the global gene expression changes by LPS and mechanism(s) by which LPS stimulates cultured hepatocytes remain uncertain. Cultures of primary mouse hepatocytes were incubated with LPS to assess its effects on the global gene expression, hepatic transcription factors, and mitogen-activated protein (MAP) kinase activation. DNA microarray analysis indicated that LPS modulates the selective expression of more than 80 genes and expressed sequence tags. We have shown previously that hepatocytes express CD14, which is required both for uptake and responsiveness to LPS. In other cells, responsiveness to microbial products requires expression of Toll-like receptors (TLR) and their associated accessory molecules. Hepatocytes expressed TLR1 through TLR9 as well as MyD88 and MD-2 transcripts, as shown by reverse transcriptase PCR analysis, indicating that hepatocytes express all known microbe recognition molecules. The MAP kinase extracellular signal-regulated kinase 1/2 was phosphorylated in response to LPS in mouse hepatocytes, and the levels of phosphorylation were lower in hepatocytes from TLR4-null mice. NF-B activation was reduced in TLR4-mutant or -null hepatocytes compared to control hepatocytes, and this defect was partially restored by adenoviral transduction of mouse TLR4. Thus, hepatocytes respond to nanogram concentrations of LPS through a TLR4 response pathway.Lipopolysaccharide (LPS), a glycolipid constituent of the outer membrane of gram-negative bacteria, initiates signaling cascades in cells such as macrophages and endothelial cells, leading to the release of cytokines and other inflammatory mediators during sepsis. Excessive production of these mediators can cause septic shock and multiple organ failure (55).A decade ago, CD14, a 55-kDa glycoprotein and monocyte differentiation antigen, was identified as an important LPS recognition molecule (60). CD14 alone, however, is unable to transduce the intracellular LPS signal, since CD14 is only tethered to the cytoplasmic membrane by a glycosyl phosphatidylinositol anchor and lacks a membrane-spanning domain (17). Members of a family of proteins, the mammalian homologues of the Drosophila Toll protein, were found to act as transmembrane coreceptors to CD14 in the cellular response to LPS (34). These Toll-like receptors (TLR) contain ectodomains with leucine-rich repeats, and their intracellular motifs are highly homologous to intracellular signaling domains of interleukin-1 receptor type I (IL-1RI) and IL-1RI accessory protein (reviewed in reference 5). Following dimerization of the TLR, these domains attract the adapter protein MyD88, which in turn recruits the IL-1R-associated kinase. Following this association, IL-1R-associated kinase phosphorylates tumor necrosis factor receptor-associated factor 6, which in turn attracts two more protein tyrosine kinases, transforming growth factor beta-activated kinase 1 (TAK-1)...

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“…In addition, hepatic macrophages respond to LPS by producing IL-8 and MCP-1, two agents which are inhibited by ␣-MSH (40). Other potential targets for ␣-MSH include hepatocytes (because LPS stimulates KC/IL-8), and Ito cells (because LPS stimulates MCP-1) (14,16,41).…”

Section: Discussionmentioning

confidence: 99%

“…MCP-1 is produced by Ito cells, and its expression is increased in toxic liver injury (14). IL-8 is increased in ethanol-treated liver and in cultured hepatocytes exposed to LPS (15,16). However, the roles of these chemokines in LPS-induced liver injury in vivo is unknown.…”

Section: Introductionmentioning

confidence: 99%

Alpha-melanocyte-stimulating hormone reduces endotoxin-induced liver inflammation.

Chiao¹,

Foster²,

Thomas³

et al. 1996

J. Clin. Invest.

138

107

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Abstract␣ -Melanocyte-stimulating hormone (MSH) is a potent antiinflammatory agent in many models of inflammation, suggesting that it inhibits a critical step common to different forms of inflammation. We showed previously that ␣ -MSH inhibits nitric oxide (NO) production in cultured macrophages. To determine how ␣ -MSH acts in vivo, we induced acute hepatic inflammation by administering endotoxin (LPS) to mice pretreated with Corynebacterium parvum . ␣ -MSH prevented liver inflammation even when given 30 min after LPS administration. To determine the mechanisms of action of ␣ -MSH, we tested its influence on NO, infiltrating inflammatory cells, cytokines, and chemokines.

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Modulation of KC/gro Protein (Interleukin-8 Related Protein in Rodents) Release from Hepatocytes by Biologically-Active Mediators

Cited by 25 publications

References 0 publications

Blocking TNF-α in mice reduces colorectal carcinogenesis associated with chronic colitis

Blocking TNF-α in mice reduces colorectal carcinogenesis associated with chronic colitis

Role of Toll-Like Receptors in Changes in Gene Expression and NF-κB Activation in Mouse Hepatocytes Stimulated with Lipopolysaccharide

Alpha-melanocyte-stimulating hormone reduces endotoxin-induced liver inflammation.

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