Lymphocyte-derived cytokines induce sequential expression of monocyte- and T cell-specific chemokines in human mesangial cells

Schwarz, Mario; Radeke, Heinfried H.; Resch, Klaus; Uciechowski, Peter

doi:10.1038/ki.1997.482

Cited by 57 publications

(49 citation statements)

References 38 publications

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“…It also proved to be of particular importance that the cells were incubated for an additional hour with repeated agitation after detachment from the flask surface, prior to antibody or biotinylated ligand incubation in order to allow receptor recovery. The fact that in this system IFNg induces both MCP-1, as we and others have previously shown [10,13], and CCR2 expression indicates a prominent role for this particular lymphokine for the regulation of mesangial cellmediated renal inflammation.…”

Section: Discussionsupporting

confidence: 77%

“…So far there are only a few reports describing the expression of chemokine receptors and their distinct functions in non-haematopoietic tissue cells, including glomerular mesangial cells [18][19][20][21]. To extend knowledge of the role of chemokines in glomerular inflammation, we investigated the expression of chemokine receptors and their functions in our well established primary human mesangial cell (HMC) culture system [1,7,8,13]. There is evidence that chemokine receptor expression in leucocytes can be regulated by inflammatory signals such as gamma-interferon (IFNg) and interleukins (IL) [22,23].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the use of HMC after passage number three excludes macrophage as well as endothelial cell contaminations because these cell types do not survive multiple passaging under the described medium conditions. After the third passage, HMC were grown, as described [4,7,13], in culture medium supporting cell proliferation consisting of RPMI-1640, NEA (1 ml/dl), Lglutamine (2 mM), sodium pyruvate (2 mM), transferrin (5 mg/ml), insulin (125 U/ml) and FCS (10%). For passaging, HMC were detached by trypsin/EDTA (0·125%/0·01%, wt/vol) and split 1:3.…”

Section: Human Glomerular Mesangial Cell Preparation Characterizatiomentioning

confidence: 99%

“…A characteristic feature of GN is the infiltration of leucocytes from the circulation into the kidney tissue, and the subsequent activation of such inflammatory cells at the site of glomerular injury. It has been demonstrated that mesangial cells are a rich source of chemokines attracting different leucocyte populations into the glomerulus [10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

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IFNγ induces functional chemokine receptor expression in human mesangial cells

Schwarz

Wahl

Resch

et al. 2002

Clinical and Experimental Immunology

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SUMMARY Infiltration of leucocyte populations into sites of inflammation is a common feature in renal diseases. Glomerular mesangial cells are potent producers of a variety of chemokines, leading to specific attraction of distinct types of inflammatory leucocytes into the glomerulus, but so far there is limited knowledge about the responsiveness of mesangial cells to chemokines. We investigated the expression of chemokine receptors and the responsiveness of primary human mesangial cells (HMC) to the chemokines which they produce, namely monocyte chemoattractant protein-1 (MCP-1) and interleukin (IL)-8. We found that mRNAs of the chemokine receptors CCR1, which has been shown before, CCR2 and CXCR2 were induced by T-helper cytokine interferon-gamma (IFNγ). In IFNγ-stimulated cells, CCR2 and CXCR2 were detectable by flow cytometry. Following treatment with IFNγ, HMC responded to MCP-1 and IL-8 with an increase of IL-6 mRNA and protein expression, which was in part blocked by pertussis toxin. Moreover, chemokine stimulation of transfected HMC led to an activation of the immunoregulatory transcription factors NFκB and AP-1. Additionally, we found that MCP-1 enhanced the expression of its own mRNA in cells activated to express CCR2, suggesting autocrine feedback mechanisms in MCP-1 regulation. Finally, IFNγ-activated cells migrated towards an MCP-1 gradient in a chemotaxis assay. These results strengthen the assumption that chemokines are not only involved in the recruitment of immune cells to inflamed tissues, but also seem to play a central role in the autocrine regulation of local tissue cells, leading to proceeding inflammation and possibly contributing to healing by mediating cell growth and migration.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Human Glomerular Mesangial Cell Preparation Characterizatiomentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

IFNγ induces functional chemokine receptor expression in human mesangial cells

Schwarz

Wahl

Resch

et al. 2002

Clinical and Experimental Immunology

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“…In addition to its potent chemotactic activity, it can induce proliferation and migration of keratinocytes, endothelial cells, and melanoma cells (Rennekampff et al, 2000;Singh and Varney, 2000;Heidemann et al, 2003). IL-8 is expressed in many different cell types, including monocytes and macrophages, endothelial cells, keratinocytes, mesangial cells, and several human tumor cell lines (Schwarz et al, 1997;Klezovitch et al, 2001;Maeda et al, 2001). Although constitutive production of IL-8 appears to be infrequent in most cell types examined, its expression can be induced in many cell types by specific stimuli such as granulocyte colony-stimulating factor, lipopolysaccharide (LPS), phorbol 12-myristate 13-acetate, viruses, and doublestranded RNA (Kasahara et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

Interleukin-1β stimulates IL-8 expression through MAP kinase and ROS signaling in human gastric carcinoma cells

et al. 2004

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Recent studies have suggested that the expression of interleukin-8 (IL-8) directly correlates with the vascularity of human gastric carcinomas. In this study, the effect of IL-1b on IL-8 expression in human gastric cancer TMK-1 cells and the underlying signal transduction pathways were investigated. IL-1b induced the IL-8 expression in a time-and concentration-dependent manner. IL-1b induced the activation of extracellular signalregulated kinases-1/2 and P38 mitogen-activated protein kinase (MAPK), but not the activation of c-jun aminoterminal kinse and Akt. Specific inhibitors of MEK-1 (PD980590) and P38 MAPK (SB203580) were found to suppress the IL-8 expression and the IL-8 promoter activity. Expression of vectors encoding a mutated-type MEK-1 and P38 MAPK resulted in decrease in the IL-8 promoter activity. IL-1b also induced the production of reactive oxygen species (ROS). N-acetyl cysteine (NAC) prevented the IL-1b-induced ROS production and IL-8 expression. In addition, exogenous H 2 O 2 could induce the IL-8 expression. Deletional and site-directed mutagenesis studies on the IL-8 promoter revealed that activator protein-1 (AP-1) and nuclear factor (NF)-jB sites were required for the IL-1b-induced IL-8 transcription. Electrophoretic mobility shift assay confirmed that IL-1b increased the DNA-binding activity of AP-1 and NF-jB. Inhibitor (PD980590, SB203580) and ROS scavenger (NAC) studies revealed that the upstream signalings for the transcription factors AP-1 and NF-jB were MAPK and ROS, respectively. Conditioned media from the TMK-1 cells pretreated with IL-1b could remarkably stimulate the in vitro growth of HUVEC and this effect was partially abrogated by IL-8-neutralizing antibodies. The above results suggest that MAPK-AP-1 and ROS-NF-jB signaling pathways are involved in the IL-1b-induced IL-8 expression and that these paracrine signaling pathways induce endothelial cell proliferation.

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IFN-γ induces the high-affinity Fc receptor I for IgG (CD64) on human glomerular mesangial cells

et al. 1998

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The deposition of immune complexes, followed by activation of complement and/or Fc receptors and generation of chemoattractants, is the most common feature of human glomerulonephritis. Recently we have shown that primary cultured human glomerular mesangial cells (HMC), which are normally negative for IgG Fc receptors, can be stimulated to express the low-affinity FcgammaRIII-A receptor isoform. In this study we further demonstrate that activation of HMC through IFN-gamma resulted in the functional expression of the high-affinity Fc receptor for IgG (FcgammaRI, CD64). IFN-gamma-dependent induction of classical FcgammaRIa1 mRNA as well as a2, b2 splice variants were evident after 24 h in proliferating HMC and after 48 h in resting HMC. Transcription of FcgammaRI mRNA was also induced by IL-10 in proliferating HMC, whereas other cytokines such as IL-3, transforming growth factor-beta1 and granulocyte-macrophage colony-stimulating factor were not effective. Cell surface expression of FcgammaRI could be detected by flow cytometric analysis after IFN-gamma stimulation and was accompanied by the augmentation of MHC class II and the up-regulation of intercellular adhesion molecule-1 expression. Triggering of HMC by cross-linking FcgammaRI with F(ab')2 fragments of the anti-CD64 monoclonal antibody 22 led to enhanced synthesis of mRNA for the chemokines IL-8 and monocyte chemoattractant protein-1, indicating that the FcgammaRI of HMC is functionally active. These in vitro data suggest that engagement of both FcgammaRI and FcgammaRIII-A on activated HMC through IgG immune complexes may result in an increased chemoattraction of leukocytes into the glomerulus, contributing to the development of glomerulonephritis.

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Lymphocyte-derived cytokines induce sequential expression of monocyte- and T cell-specific chemokines in human mesangial cells

Cited by 57 publications

References 38 publications

IFNγ induces functional chemokine receptor expression in human mesangial cells

IFNγ induces functional chemokine receptor expression in human mesangial cells

Interleukin-1β stimulates IL-8 expression through MAP kinase and ROS signaling in human gastric carcinoma cells

IFN-γ induces the high-affinity Fc receptor I for IgG (CD64) on human glomerular mesangial cells

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