STAT1 is Constitutively Activated in the T/C28a2 Immortalized Juvenile Human Chondrocyte Line and Stimulated by IL-6 Plus Soluble IL-6R

Meszaros, Evan; Malemud, Charles J.

doi:10.4172/2155-9899.1000307

Cited by 4 publications

(3 citation statements)

References 54 publications

(54 reference statements)

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“…We also showed western blots at Immunology summit-2015 demonstrating that STAT1 was constitutively phosphorylated in the T/C28a2 chondrocyte line [ 16 ]. However, C-28/I2 chondrocytes incubated with rhIL-6 (50 ng/ml) resulted in the phosphorylation of STAT3 without changing total STAT3 [ 15 ].…”

Section: Resultsmentioning

confidence: 99%

“…We had previously shown using a quantitative immunoblot analysis that rhIL-6, rhTNF-α or sIL-6R activated STAT3 protein in human immortalized chondrocyte cell lines [ 15 , 16 ]. We had also shown that incubating human chondrocytes enzymatically liberated from OA knee cartilage with rhTNF-α (10 ng/ml) resulted in the phosphorylation of U-STAT3 (p-STAT3) without altering total U-STAT3α [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Matrix Metalloproteinase-9 Production by Immortalized Human Chondrocyte Lines

Malemud

Meszaros

Wylie

et al. 2016

J Clin Cell Immunol

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We reported at the Keynote Forum of Immunology Summit-2015 that recombinant human (rh) TNF-α or rhIL-6 stimulated production of matrix metalloproteinase-9 (MMP-9) in the T/C28a2 and C-28/I2 human immortalized chondrocyte cell lines. Furthermore, we reported that tocilizumab (TCZ), a fully humanized monoclonal antibody which neutralizes IL-6-mediated signaling, inhibited the rhIL-6-mediated increase in the production of MMP-9. IL-6 is also a known activator of the JAK/STAT signaling pathway. In that regard, we evaluated the effect of rhIL-6 on total and phosphorylated Signal Transducer and Activator of Transcription by these chondrocyte lines which showed that whereas STAT3 was constitutively phosphorylated in T/C28a2 chondrocytes, rhIL-6 activated STAT3 in C-28/I2 chondrocytes. The finding that rhIL-6 increased the production of MMP-9 by human immortalized chondrocyte cell lines may have important implications with respect to the destruction of articular cartilage in rheumatoid arthritis and osteoarthritis. Thus, the markedly elevated level of IL-6 in rheumatoid arthritis and osteoarthritis sera and synovial fluid would be expected to generate significant MMP-9 to cause the degradation of articular cartilage extracellular matrix proteins. The finding that TCZ suppressed rhIL-6-mediated MMP-9 production suggests that TCZ, currently employed in the medical therapy of rheumatoid arthritis, could be considered as a drug for osteoarthritis.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Matrix Metalloproteinase-9 Production by Immortalized Human Chondrocyte Lines

Malemud

Meszaros

Wylie

et al. 2016

J Clin Cell Immunol

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“…All these cells were cultured in specific medium (Invitrogen, Carlsbad, CA, USA) supplemented with 10% (v/v) fetal bovine serum (FBS, Invitrogen), 100 μg/ml streptomycin, and 100U/ml penicillin (Invitrogen) at 37 °C with 5% CO 2 . Cells were serum starved for 12 h prior to EGF (10 ng/ml), insulin (100 nmol/l), TGF-β (5 ng/ml), IL-6 (50 ng/ml), and estradiol (10 nM) treatment for 6 hours36373839. Culture medium was switched to serum-free and phenol red-free medium to avoid potential interference from serum hormones or phenol red.…”

Section: Methodsmentioning

confidence: 99%

Cholesterol Synthetase DHCR24 Induced by Insulin Aggravates Cancer Invasion and Progesterone Resistance in Endometrial Carcinoma

Dai

Zhu

Liu

et al. 2017

Sci Rep

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3β-Hydroxysteroid-Δ24 reductase (DHCR24), the final enzyme of the cholesterol biosynthetic pathway, has been associated with urogenital neoplasms. However, the function of DHCR24 in endometrial cancer (EC) remains largely elusive. Here, we analyzed the expression profile of DHCR24 and the progesterone receptor (PGR) in our tissue microarray of EC (n = 258), the existing EC database in GEO (Gene Expression Omnibus), and TCGA (The Cancer Genome Atlas). We found that DHCR24 was significantly elevated in patients with EC, and that the up-regulation of DHCR24 was associated with advanced clinical stage, histological grading, vascular invasion, lymphatic metastasis, and reduced overall survival. In addition, DHCR24 expression could be induced by insulin though STAT3, which directly binds to the promoter elements of DHCR24, as demonstrated by ChIP-PCR and luciferase assays. Furthermore, genetically silencing DHCR24 inhibited the metastatic ability of endometrial cancer cells and up-regulated PGR expression, which made cells more sensitive to progestin. Taken together, we have demonstrated for the first time the crucial role of the insulin/STAT3/DHCR24/PGR axis in the progression of EC by modulating the metastasis and progesterone response, which could serve as potential therapeutic targets for the treatment of EC with progesterone receptor loss.

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Phosphorylation of STAT proteins by recombinant human IL-6 in immortalized human chondrocyte cell lines, T/C28a2 and C28/I2

Meszaros

Malemud

2017

JIR

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Two immortalized human juvenile chondrocyte cell lines, T/C28a2 and C28/I2, were employed to determine the extent to which recombinant human (rh) IL-6, a known cytokine activator of the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway in many cell types, caused STAT proteins to be phosphorylated. The results showed that STAT3 was constitutively phosphorylated in the absence of rhIL-6 in T/C28a2 chondrocytes. However, C28/I2 chondrocytes treated with rhIL-6 caused STAT1, STAT3, and STAT5 to be phosphorylated without altering total unphosphorylated STAT proteins. STAT3 phosphorylation in response to rhIL-6 in T/C28a and C28/I2 chondrocytes was efficiently blocked by the JAK3-selective inhibitor WHI-P131 (Janex-1) and by soluble IL-6 receptor-α (sIL-6R). However, the combination of rhIL-6 and ruxolitinib, a JAK1/JAK2-selective inhibitor, was a less effective inhibitor of STAT protein activation. These findings showed that rhIL-6 activated STAT proteins in the C28/I2 chondrocyte cell line. STAT protein phosphorylation could be blocked by a JAK3-selective inhibitor or by the combination of rhIL-6 and sIL-6R.

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STAT1 is Constitutively Activated in the T/C28a2 Immortalized Juvenile Human Chondrocyte Line and Stimulated by IL-6 Plus Soluble IL-6R

Cited by 4 publications

References 54 publications

Matrix Metalloproteinase-9 Production by Immortalized Human Chondrocyte Lines

Matrix Metalloproteinase-9 Production by Immortalized Human Chondrocyte Lines

Cholesterol Synthetase DHCR24 Induced by Insulin Aggravates Cancer Invasion and Progesterone Resistance in Endometrial Carcinoma

Phosphorylation of STAT proteins by recombinant human IL-6 in immortalized human chondrocyte cell lines, T/C28a2 and C28/I2

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