Interleukin 6 and expression of its receptor on epidermal keratinocytes

Yoshizaki, Kazuyuki; Nishimoto, Norihiro; Matsumoto, Kunio; Tagoh, Hiromi; Taga, Tetsuya; Deguchi, Yasuo; Kuritani, Taro; Hirano, Toshio; Hashimoto, Kunihiko; Okada, Natsuko

doi:10.1016/1043-4666(90)90069-6

Cited by 77 publications

(44 citation statements)

References 29 publications

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“…While knowledge about the differentiation and proliferation of epidermal keratinocytes is expanding rapidly, there are only sparse reports about the functional capacity of keratinocytes derived from mucosa [26]. Nearly all functional studies on keratinocytes are carried out with subcultivated cells [12,18,27]. Subcultivation usually means the adherence of cells, confluency and various times of culture.…”

Section: Introductionmentioning

confidence: 99%

Magnetic cell separation for purification of human oral keratinocytes: an effective method for functional studies without prior cell subcultivation

Formanek

Temmel

Knerer

et al. 1998

European Archives of Oto-Rhino-Laryngology

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In studying human oral keratinocytes, it would be very helpful to obtain a pure population of cells without prior in vitro expansion. An immunomagnetic separation technique, or magnetic cell separation (MACS), was modified for efficient purification of human oral keratinocytes. Subsequent to two-step enzymatic digestion, the cell suspension was labelled with a mouse anti-CD45 (pan-leukocyte) monoclonal antibody (MoAb) to stain mononuclear cells. In a second step a rat anti-mouse antibody conjugated with colloidal superparamagnetic particles was used. Labelled cells were retained in the magnetic field of a permanent magnet on columns containing a ferromagnetic matrix. The unlabelled, unretained cells were further examined by flow cytometry analysis, enzyme-linked immunosorbent assay and polymerase chain reaction. After the MACS procedure, unretained cells showed a strong positivity for the lu-5 MoAb (as a marker for pan-cytokeratin) and were negative for anti-vimentin (to mark mesenchymal cells), for anti-CD45 MoAb and for melanocyte-detecting antibodies, thus representing pure keratinocytes (> 98%). Purified keratinocytes maintained full viability (> 91%) and functional capacities. [3H]thymidine uptake and epidermal growth factor (EGF) receptor expression were unaltered when compared with the non-separated cell population. Furthermore, interleukin-1 alpha was detected at the protein and RNA levels in keratinocytes immediately after MACS enrichment. Our findings show that MACS appears to be a useful tool for purification of oral keratinocytes and allows for further functional studies without prior subcultivation of cells.

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Section: Introductionmentioning

confidence: 99%

Magnetic cell separation for purification of human oral keratinocytes: an effective method for functional studies without prior cell subcultivation

Formanek

Temmel

Knerer

et al. 1998

European Archives of Oto-Rhino-Laryngology

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“…Several chemokines and cytokines, including IL-6 and IL-8, are expressed in both primary and immortalized vaginal and cervical epithelial cells, aiding in both innate and adaptive immunity (6, 9 -13). In the cervix, IL-6 gene expression can be induced by pathogen infection (14,15) and exposure to pro-inflammatory cytokines such as TNF␣ (16,17). IL-6 activates T-cells, causing them to differentiate, and also plays a role in cervical dilation and tumor angiogenesis (18,19).…”

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confidence: 99%

Glucocorticoid-independent Repression of Tumor Necrosis Factor (TNF) α-stimulated Interleukin (IL)-6 Expression by the Glucocorticoid Receptor

Verhoog

Toit

Avenant

et al. 2011

Journal of Biological Chemistry

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TNF␣ signaling and cytokine levels play a crucial role in cervical immunity and the host response to infections. We investigated the role of liganded and unliganded glucocorticoid receptor (GR) in IL-6 and IL-8 gene regulation in response to TNF␣ in the End1/E6E7 immortalized human endocervical epithelial cell line. In the absence of glucocorticoids, both decreasing GR protein levels by an siRNA strategy and results with the GR antagonist RU486 suggest a role for the unliganded GR in reduction of TNF␣-induced IL-6 and IL-8 mRNA levels in End1/E6E7 cells. Moreover, GR-dependent repression of endogenous IL-6 mRNA as well as a minimal IL-6 promoter-reporter gene is also demonstrated in COS-1 cells in the absence of GR ligand, suggesting a transcriptional mechanism that is not cell-specific. TNF␣ induced recruitment of both the unliganded GR and GRinteracting protein type 1 (GRIP-1) to the IL-6 promoter. This, together with GRIP-1 overexpression studies, suggests a function for GRIP-1 as a GR co-repressor in this context. TNF␣ was shown to induce phosphorylation of the unliganded human GR at Ser-226 but not Ser-211, unlike dexamethasone, which induced hyperphosphorylation at both serine residues. Ser-226 is shown to be required for the ligand-independent GR-mediated repression of IL-6 in response to TNF␣. Taken together, these results support a model whereby the unliganded GR attenuates TNF␣-stimulated IL-6 transcription by a mechanism involving selective phosphorylation and recruitment of the unliganded GR and GRIP-1 to the IL-6 promoter. These findings suggest the presence of a novel autoregulatory mechanism that may prevent overproduction of IL-6 in the endocervix, possibly protecting against negative effects of excessive inflammation.

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“…Leukocytosis and fever have been found to be the result of increased production of IL-6 in vivo (16). In addition, IL-6 can induce the proliferation of mesangial cells (17), epidermal keratinocytes (18), and various tumor cells such as malignant lymphomacells, multiple myelomacells, and renal carcinoma cells (6), as well as the differentiation of osteoclasts (19). From a study using IL-6 transgenic mice, we have been able to learn what kinds of abnormalities the hyperproduction ofIL-6 can cause in vivo.…”

Section: Introductionmentioning

confidence: 99%