title: IL-17A stimulates granulocyte colony-stimulating factor production via ERK1/2 but not p38 or JNK in human renal proximal tubular epithelial cells.
abstract: We investigated the potential role of IL-17A in the induction of granulocyte colony-stimulating factor (G-CSF), a critical granulopoietic growth factor, in human renal proximal tubular epithelial cells. Human renal proximal tubular cells (HK-2, ATCC) were used to characterize the effects of IL-17A or IL-17F on G-CSF production, using ELISA, real-time RT-PCR, and immunoblotting. The cell surface expression of IL-17 receptors (IL-17Rs) was analyzed by flow cytometry. IL-17A stimulation of proximal tubular cells led to a dose- and time-dependent increase in secreted G-CSF. This effect was dependent on mRNA transcription and protein translation. Real-time RT-PCR demonstrated that G-CSF mRNA expression reached a maximum level at 6 h following IL-17A stimulation and that this increase was dose dependent. Both IL-17RA and IL-17RC were expressed on proximal tubular cells. IL-17A also enhanced TNF-α- or IL-1β-mediated G-CSF secretion from cells. Additionally, IL-17A induced MAPK (ERK1/2 but not p38 MAPK or JNK) activation, and pharmacological inhibitors of MEK1/2 (U0126) but not of p38 MAPK (SB203580) or JNK (SP600125), significantly blocked the IL-17A-mediated G-CSF release. We demonstrated the potential ability of IL-17A to induce G-CSF in renal proximal tubular cells. It is proposed that IL-17A may play an important role in neutrophil transmigration and activation via stimulation of G-CSF in tubular injury.
authors: Div. of Nephrology, Dept. of Medicine, Showa Univ. School of Medicine, Hatanodai, Shinagawa-ku, Tokyo, Japan.
authors: Yuki
authors: Y
authors: Hirai
authors: Masayuki
authors: M
authors: Iyoda
authors: Takanori
authors: T
authors: Shibata
authors: Yoshihiro
authors: Y
authors: Kuno
authors: Mio
authors: M
authors: Kawaguchi
authors: Nobuyuki
authors: N
authors: Hizawa
authors: Kei
authors: K
authors: Matsumoto
authors: Yukihiro
authors: Y
authors: Wada
authors: Fumio
authors: F
authors: Kokubu
authors: Tadao
authors: T
authors: Akizawa
mesh_terms: D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis*; D006801:Humans; D020381:Interleukin-17 / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D053722:Receptors, Interleukin-17 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D020381:Interleukin-17; D053583:Interleukin-1beta; D053722:Receptors, Interleukin-17; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4