Binding of the chemokine SLC/CCL21 to its receptor CCR7 increases adhesive properties of human mesangial cells

Banas, Bernhard; Wörnle, Markus; Merkle, Monika; González-Rubio, Mercedes; Schmid, Holger; Kretzler, Matthias; Pietrzyk, Miriam; Fink, Monika; Lema, Guillermo Pérez de; Schlöndorff, Detlef

doi:10.1111/j.1523-1755.2004.66037.x

Cited by 22 publications

(33 citation statements)

References 43 publications

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“…Interestingly, we could show low basal expression levels of APRIL mRNA in cultured mesangial cells. 30 However, we could not demonstrate increased APRIL mRNA expression by this cell line under proinflammatory stimulation. As the glomerular APRIL expression is only found in ISN/ RPS III and IV lupus nephritis, but not in ISN/RPS V, we may have failed to sufficiently mimic the specific glomerular milieu of proinflammatory mediators or stimulation by immune complexes.…”

Section: Discussioncontrasting

confidence: 67%

“…In cultured mesangial cells, very low basal mRNA expression for APRIL was found (mean C t -value: 36±1; n ¼ 3). 30 No rise in APRIL mRNA was seen under proinflammatory stimulation with IFN-a, -b, -g, IL-2, and human TNF-a (data not shown).…”

Section: Cell Culturementioning

confidence: 91%

“…Human mesangial cells 30 were cultured as previously reported. Except for controls they were stimulated with the indicated reagents and concentrations (n ¼ 3 or n ¼ 4 wells for each condition): universal type 1 interferon (IFN)-a (1000 U/ml; PBL InterferonSource, NJ, USA), recombinant human interferon IFN-b (1000 U/ml; R&D Systems, Abingdon, UK), recombinant human IFN-g (1000 U/ml; R&D Systems), recombinant human interleukin (IL)-2 (5 ng/ml; R&D Systems) and recombinant human TNF-a (25 ng/ml; R&D Systems).…”

Section: Cell Culturementioning

confidence: 99%

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Intrarenal production of B-cell survival factors in human lupus nephritis

et al. 2011

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The B-cell survival factors APRIL and BLyS are important for B-cell maturation and activation and contribute to human autoimmune diseases. Interference with B-cell function by targeting these molecules is currently being investigated in large clinical trials for systemic lupus erythematosus. The local expression patterns of APRIL and BLyS have not been investigated in detail in kidneys with lupus nephritis. We studied the mRNA expression of APRIL, BLyS, and the corresponding receptors BCMA, TACI, and BAFF-R in microdissected human biopsies with proliferative lupus nephritis (n ¼ 25) and compared it with pretransplant biopsies of living donors (n ¼ 9). APRIL and BLyS mRNA levels were significantly higher in glomeruli of patients with proliferative lupus nephritis (12-and 30-fold, respectively). Tubulointerstitial expression of APRIL, BLyS, BCMA, and TACI was also significantly elevated. To localize the respective proteins in the kidney, APRIL, BLyS, and BAFF-R were studied by immunohistochemistry in renal biopsies with proliferative (n ¼ 21) or membranous (n ¼ 8) lupus nephritis. APRIL was prominently expressed in glomeruli with proliferative, but not membranous, lupus nephritis. The staining pattern was consistent with mesangial cells. A prominent accumulation of CD68-positive cells was present in glomeruli in association with APRIL expression. APRIL, BLyS, and BAFF-R were also expressed in interstitial inflammatory cell accumulation. This is the first study, which details local expression of APRIL and BLyS in glomeruli and tubulointerstitium of human proliferative lupus nephritis. This information might help define intrarenal effects of APRIL and BLyS inhibition in human lupus nephritis.

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Section: Discussioncontrasting

confidence: 67%

Section: Cell Culturementioning

confidence: 91%

Section: Cell Culturementioning

confidence: 99%

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Intrarenal production of B-cell survival factors in human lupus nephritis

et al. 2011

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“…Our western blot analysis shows that stimulation with ccL19 also resulted in increased phosphorylation of αvβ3 integrin, an effect which was blocked by the ccR7 mAb and the IS201 inhibitor (Fig. 5), in accordance to previous studies (21,23). β1 integrin may indeed be the pertinent downstream target of the ccR7 pathway in this system.…”

Section: Discussionsupporting

confidence: 70%

“…ccL21 promotes the migration and adhesion of lymph node metastases of human non-small cell lung cancer via integrins (22). Binding of the chemokine ccL19/ccL21 to its receptor, ccR7, increases adhesive properties of human mesangial cells by regulating integrins (23).…”

Section: Introductionmentioning

confidence: 99%

Chemokine receptor 7 promotes cell migration and adhesion in metastatic squamous cell carcinoma of the head and neck by activating integrin αvβ3

Liu¹,

Sun²,

Zhao³

et al. 2011

Int J Mol Med

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Abstract. The mechanisms leading to squamous cell carcinoma of the head and neck (SccHN) metastasis are incompletely understood. Although evidence shows that the chemokine receptor 7 (ccR7) and its ligand ccL19 may regulate tumor dissemination, their role in SCCHN is not clearly defined. CCR7 has been shown to regulate integrins, which facilitate adhesion of cancer cells to and/or migration through the extracellular matrix (EcM). To investigate the relationship between ccR7 and integrin αvβ3 in metastatic SccHN, we used adhesion and migration assays, immunofluorescence staining and western blotting to determine whether integrin αvβ3 can be activated by ccL19 in the metastatic SccHN cell line PcI-37B, which was pre-incubated with ccL19 or the integrin αvβ3 inhibitor, IS201. Our results demonstrate that ccR7 favors PcI-37B cell adhesion and migration, induces reorganization of the actin cytoskeleton and induces integrin αvβ3 phosphorylation. The integrin αvβ3 inhibitor, IS201, blocked all of these effects. ccR7 and integrin αvβ3 expression significantly and positively correlated with tumor size, clinical stage and nodal metastasis. Taken together, our data indicate that ccR7 regulates cell adhesion and migration via integrin αvβ3 in metastatic SccHN. These results should provide the groundwork for new strategies aimed at preventing SccHN metastasis.

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Chemokine receptors in tissue cells and angiogenesis

Romagnani

Lasagni

Romagnani

Chemokine Biology — Basic Research and Clinical Application

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Binding of the chemokine SLC/CCL21 to its receptor CCR7 increases adhesive properties of human mesangial cells

Cited by 22 publications

References 43 publications

Intrarenal production of B-cell survival factors in human lupus nephritis

Intrarenal production of B-cell survival factors in human lupus nephritis

Chemokine receptor 7 promotes cell migration and adhesion in metastatic squamous cell carcinoma of the head and neck by activating integrin αvβ3

Chemokine receptors in tissue cells and angiogenesis

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