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TNF and IL‐6/STAT3 crosstalk revealed in a commercially‐available cell line
Author(s) -
Loring Ralph H,
Naiki Pranitha,
Wu Ting,
Garg Brijesh
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb552
Subject(s) - tumor necrosis factor alpha , crosstalk , hek 293 cells , secretion , interleukin 6 , stat3 , cytokine , microbiology and biotechnology , chemistry , cell culture , proinflammatory cytokine , signal transduction , endocrinology , medicine , inflammation , biology , immunology , physics , genetics , optics
TNF (Tumor necrosis factor alpha) and IL‐6 (Interleukin 6) are cytokines with important inflammation and cancer roles that exhibit different interactions depending on cell context, e.g. TNF sometimes induces IL‐6 secretion, but TNF also directly alters IL‐6 signaling and vice versa (crosstalk). IL‐6 activates the transcription factor STAT3 in HEK‐Blue® IL‐6 cells (Invivogen) and STAT3 stimulates a reporter gene, secreted alkaline phosphatase (AP), but STAT3 inhibitors block AP secretion. Co‐application of 0.3–10 ng/ml TNF increases IL‐6 induced AP secretion 2–5 fold. However, TNF alone has no effect on basal STAT3 signaling, suggesting that TNF increases IL‐6 sensitivity without inducing IL‐6 secretion. SN50, an inhibitor of the transcription factor NFkB, does not block TNF changes in IL‐6 sensitivity, suggesting a different TNF signaling pathway. TNF effects originally appeared in HEK‐Blue® cells grown in medium giving unusually low responses to IL‐6, and the effects are retained in serum‐free medium. TNF effects on HEK‐Blue® cells grown in chemically‐defined medium may lead to finding serum factors that influence the context of TNF and IL‐6 crosstalk. No external funding.