Abstract
IL-27 is a pleiotropic cytokine of the IL-6/IL-12 family with diverse biological functions. Previous in vivo studies have suggested the antitumor activities of IL-27 in animal models, whereas clinical observations indicate the link of IL-27 in tumor progression. IL-27 has recently been shown to cause inhibition of proliferation on primary leukemic cells from pediatric patients, but information on its role in human leukemic cell lines is limited. In the present study, we investigated the ability of IL-27 to regulate cell growth and survival of various human leukemic cell lines. Our results showed that in human leukemic cell lines coexpressing both IL-27R chains, IL-27Rα and gp130, IL-27 did not inhibit cell growth, but caused dose-dependent proliferation of the acute myeloid leukemic cell line, OCI-AML5, and the erythroleukemic cell lines, TF-1, UT-7, and UT-7/EPO. Consistent with this, IL-27 promoted cell survival and reduced TNF-α-induced apoptosis of the leukemic cell lines. IL-27 also decreased the responsiveness of the leukemic cells to chemotherapeutic drugs, cytarabine and daunorubicin. We observed that IL-27 induced the activation of STAT1/3 and ERK1/2 in the leukemic cells. Growth stimulation by IL-27 was suppressed by the specific MEK inhibitor, U0126, indicating that IL-27-induced cell proliferation is mainly mediated through the activation of the MAPK/ERK signaling pathway. The present study is the first demonstration of the proliferative and antichemotherapeutic properties of IL-27 in human leukemic cell lines, suggesting that IL-27 can play an unfavorable role in tumor growth and can be an important determinant in the chemoresponsiveness of certain subtypes of human leukemia.
Highlights
Interleukin-27 is a heterodimeric cytokine of the IL-6/ IL-12 family comprising the cytokine subunit p28 and the soluble cytokine receptor Epstein–Barr virus-induced gene 3 (EBI3) (Pflanz and others 2002)
We first examined the expression of both chains, IL-27Ra and gp[130], of IL-27R on a panel of nine tumor cell lines, including 4 acute myeloid leukemia (AML) cell lines (HL-60, KG-1, OCI-AML5, U937), 3 erythroleukemic cell lines (TF-1, UT-7, UT-7/ EPO), an acute T-cell leukemic cell line ( Jurkat), and a melanoma cell line (A375) at both mRNA and cell surface levels to identify IL-27R-positive tumor cell lines
Seven leukemic cell lines showed the presence of both IL-27 chains, suggesting these cell lines may respond to IL-27 modulation in their cellular activities
Summary
Interleukin-27 is a heterodimeric cytokine of the IL-6/ IL-12 family comprising the cytokine subunit p28 and the soluble cytokine receptor Epstein–Barr virus-induced gene 3 (EBI3) (Pflanz and others 2002). Produced by activated antigen-presenting cells, including dendritic cells and macrophages upon exposure to physiological stimuli, IL-27 signals through a heterodimeric receptor consisting of 2 chains, the specific IL-27Ra (WSX-1 or TCCR) paired with the signal-transducing gp[130] that is shared by the IL-6 family of cytokines (Pflanz and others 2004), and activates the signal transducer and activator of transcription (STAT) pathway. IL-27R components are expressed on a wide variety of immune, hematopoietic, endothelial, and epithelial cells, resulting in a variety of cellular targets and diverse functions for its ligand. IL-27 functions as a pleiotropic cytokine that is capable of modulating immune response, inflammation, hematopoiesis, and tumor growth (Hunter and Kastelein 2012; Adamopoulos and Pflanz 2013). IL-27 plays a dual role in the regulation of inflammation by immunostimulatory or immunosuppressive functions on target cells (Yoshida and others 2009; Hunter and Kastelein 2012)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
