Interleukin-13 Inhibits Cell Proliferation and Stimulates Interleukin-6 Formation in Isolated Human Osteoblasts

To investigate whether palmitic acid can be responsible for the induction of inflammatory processes, HaCaT keratinocytes were treated with palmitic acid at pathophysiologically relevant concentrations. Secretion levels of interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), NF-κB nuclear translocation, NF-κB activation, Stat3 phosphorylation, and peroxisome proliferator-activated receptor alpha (PPARα) mRNA and protein levels, as well as the cell proliferation ability were measured at the end of the treatment and after 24 hours of recovery. Pyrrolidine dithiocarbamate (PDTC, a selective chemical inhibitor of NF-κB) and goat anti-human IL-6 polyclonal neutralizing antibody were used to inhibit NF-κB activation and IL-6 production, respectively. Our results showed that palmitic acid induced an upregulation of IL-6, TNF-α, IL-1βsecretions, accompanied by NF-κB nuclear translocation and activation. Moreover, the effect of palmitic acid was accompanied by PPARαactivation and Stat3 phosphorylation. Palmitic acid-induced IL-6, TNF-α, IL-1βproductions were attenuated by NF-κB inhibitor PDTC. Palmitic acid was administered in amounts able to elicit significant hyperproliferation and can be attenuated by IL-6 blockage. These data demonstrate for the first time that palmitic acid can stimulate IL-6, TNF-α, IL-1βproductions in HaCaT keratinocytes and cell proliferation, thereby potentially contributing to acne inflammation and pilosebaceous duct hyperkeratinization.

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Stress hormones increase cell proliferation and regulates interleukin-6 secretion in human oral squamous cell carcinoma cells

Brain Behavior and Immunity ◽

10.1016/j.bbi.2010.12.012 ◽

2011 ◽

Vol 25 (3) ◽

pp. 574-583 ◽

Cited By ~ 61

Author(s):

Daniel G. Bernabé ◽

Adriano C. Tamae ◽

Éder R. Biasoli ◽

Sandra H.P. Oliveira

Keyword(s):

Cell Proliferation ◽

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Interleukin 6 ◽

Stress Hormones ◽

Carcinoma Cells

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Requirements of src family kinase activity associated with CD45 for myeloma cell proliferation by interleukin-6

Blood ◽

10.1182/blood.v99.6.2172 ◽

2002 ◽

Vol 99 (6) ◽

pp. 2172-2178 ◽

Cited By ~ 57

Author(s):

Hideaki Ishikawa ◽

Naohiro Tsuyama ◽

Saeid Abroun ◽

Shangqin Liu ◽

Fu-Jun Li ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Lines ◽

Interleukin 6 ◽

Kinase Inhibitor ◽

Myeloma Cell ◽

Src Family Kinases ◽

Src Family Kinase ◽

Receptor Complexes ◽

Intracellular Signals ◽

Cellular Context

Abstract Specific intracellular signals mediated by interleukin-6 (IL-6) receptor complexes, such as signal transducer and activator of transcription 3 (STAT 3) and extracellular signal–regulated kinase (ERK) 1/2, are considered to be responsible for inducing a variety of cellular responses. In multiple myeloma, IL-6 only enhanced the proliferation of CD45+ tumor cells that harbored the IL-6–independent activation of src family kinases even though STAT3 and ERK1/2 could be activated in response to IL-6 in both CD45+ and CD45− cells. Furthermore, the IL-6–induced proliferation of CD45+ U266 myeloma cells was significantly suppressed by Lyn-specific antisense oligodeoxynucleotides or a selective src kinase inhibitor. These results indicate that the activation of both STAT3 and ERK1/2 is not enough for IL-6–induced proliferation of myeloma cell lines that require src family kinase activation independent of IL-6 stimulation. Thus, the activation of the src family kinases associated with CD45 expression is a prerequisite for the proliferation of myeloma cell lines by IL-6. We propose a mechanism for IL-6–induced cell proliferation that is strictly dependent upon the cellular context in myelomas.

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Effect of interleukin-6 receptor blockage on renal injury in apolipoprotein E-deficient mice

AJP Renal Physiology ◽

10.1152/ajprenal.90680.2008 ◽

2009 ◽

Vol 297 (3) ◽

pp. F679-F684 ◽

Cited By ~ 30

Author(s):

Mari Tomiyama-Hanayama ◽

Hiromi Rakugi ◽

Masaharu Kohara ◽

Toru Mima ◽

Yasuo Adachi ◽

...

Keyword(s):

Cell Proliferation ◽

Apolipoprotein E ◽

Interleukin 6 ◽

Renal Injury ◽

Mesangial Cell ◽

Organ Damage ◽

Glomerular Injury ◽

Mesangial Cell Proliferation ◽

Matrix Expansion ◽

Interleukin 6 Receptor

Hyperlipidemia has been demonstrated to be associated with renal disease, yet the mechanism of renal injury is still poorly understood. Inflammation that occurs with the hyperlipidemia has been considered to play an important role in development of glomerular injury. In the present study, we investigated the role of interleukin-6 (IL-6), a key inflammatory molecule, on renal injury in apolipoprotein E-deficient (ApoE−/−) mice with severe hypercholesterolemia. The 6-wk-old mice were fed a high-fat diet and administered weekly rat anti-IL-6 receptor monoclonal antibody (MR16-1), control rat IgG, or saline for a total of 4 wk. We examined histopathological changes in the kidney and urinary excretion of protein and albumin. Saline- and IgG-treated mice showed remarkable proteinuria at 10 wk of age, whereas MR16-1-treated mice exhibited significantly lower levels. Renal histopathology of saline- and IgG-treated mice revealed striking lipid deposits and foam cells in the glomerular tuft, juxtaglomerular area, and arteriolar wall along with range of mesangial cell proliferation and matrix expansion. Notably, the severity of lipid deposits and mesangial cell proliferation were significantly reduced in MR16-1-treated mice. Immunohistochemistry demonstrated that mesangial IL-6 expression was dramatically reduced in MR16-1-treated mice compared with IgG-treated mice. Blocking the IL-6 receptor prevented progression of proteinuria and renal lipid deposit, as well as the mesangial cell proliferation associated with severe hyperlipoproteinemia. These results clearly demonstrate that IL-6 plays an essential role in the pathogenesis of hyperlipidemia-induced glomerular injury in ApoE−/− mice and suggests the usefulness of anti-IL-6 receptor antibody in treatments for hyperlipidemia-induced organ damage.

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