title: IL22/IL-22R pathway induces cell survival in human glioblastoma cells.
abstract: Interleukin-22 (IL-22) is a member of the IL-10 cytokine family that binds to a heterodimeric receptor consisting of IL-22 receptor 1 (IL-22R1) and IL-10R2. IL-22R expression was initially characterized on epithelial cells, and plays an essential role in a number of inflammatory diseases. Recently, a functional receptor was detected on cancer cells such as hepatocarcinoma and lung carcinoma, but its presence was not reported in glioblastoma (GBM). Two GBM cell lines and 10 primary cell lines established from patients undergoing surgery for malignant GBM were used to investigate the expression of IL-22 and IL-22R by using quantitative RT-PCR, western blotting and confocal microscopy studies. The role of IL-22 in proliferation and survival of GBM cell lines was investigated in vitro by BrdU and ELISA cell death assays. We report herein that the two subunits of the IL-22R complex are expressed on human GBM cells. Their activation, depending on exogenous IL-22, induced antiapoptotic effect and cell proliferation. IL-22 treatment of GBM cells resulted in increased levels of phosphorylated Akt, STAT3 signaling protein and its downstream antiapoptotic protein Bcl-xL and decreased level of phosphorylated ERK1/2. In addition, IL-22R subunits were expressed in all the 10 tested primary cell lines established from GBM tumors. Our results showed that IL-22R is expressed on GBM established and primary cell lines. Depending on STAT3, ERK1/2 and PI3K/Akt pathways, IL-22 induced GBM cell survival. These data are consistent with a potential role of IL-22R in tumorigenesis of GBM. Since endogenous IL-22 was not detected in all studied GBM cells, we hypothesize that IL-22R could be activated by immune microenvironmental IL-22 producing cells.
authors: Laboratoire Homéostasie Cellulaire et Pathologies (LHCP-EA 3842), Faculté de Médecine et de Pharmacie, Université de Limoges, Limoges, France.
authors: Hussein
authors: H
authors: Akil
authors: Laboratoire Homéostasie Cellulaire et Pathologies (LHCP-EA 3842), Faculté de Médecine et de Pharmacie, Université de Limoges, Limoges, France.
authors: Amazigh
authors: A
authors: Abbaci
authors: Laboratoire Homéostasie Cellulaire et Pathologies (LHCP-EA 3842), Faculté de Médecine et de Pharmacie, Université de Limoges, Limoges, France.
authors: Fabrice
authors: F
authors: Lalloué
authors: Laboratoire Homéostasie Cellulaire et Pathologies (LHCP-EA 3842), Faculté de Médecine et de Pharmacie, Université de Limoges, Limoges, France.
authors: Barbara
authors: B
authors: Bessette
authors: Laboratoire Homéostasie Cellulaire et Pathologies (LHCP-EA 3842), Faculté de Médecine et de Pharmacie, Université de Limoges, Limoges, France.
authors: Léa M M
authors: LM
authors: Costes
authors: Laboratoire Homéostasie Cellulaire et Pathologies (LHCP-EA 3842), Faculté de Médecine et de Pharmacie, Université de Limoges, Limoges, France.
authors: Linda
authors: L
authors: Domballe
authors: Laboratoire Inflammation, Tissus Epithéliaux et Cytokines (LITEC-EA 4331), Université de Poitiers, Poitiers, France.
authors: Sandrine
authors: S
authors: Charreau
authors: INSERM U1084, Université de Poitiers, Poitiers, France; Laboratoire de Cancérologie Biologique, CHU de Poitiers, Poitiers, France.
authors: Karline
authors: K
authors: Guilloteau
authors: INSERM U1084, Université de Poitiers, Poitiers, France; Laboratoire de Cancérologie Biologique, CHU de Poitiers, Poitiers, France.
authors: Lucie
authors: L
authors: Karayan-Tapon
authors: Laboratoire Inflammation, Tissus Epithéliaux et Cytokines (LITEC-EA 4331), Université de Poitiers, Poitiers, France; BIOalternatives, Gençay, France.
authors: François-Xavier
authors: FX
authors: Bernard
authors: Laboratoire Inflammation, Tissus Epithéliaux et Cytokines (LITEC-EA 4331), Université de Poitiers, Poitiers, France.
authors: Franck
authors: F
authors: Morel
authors: Laboratoire Homéostasie Cellulaire et Pathologies (LHCP-EA 3842), Faculté de Médecine et de Pharmacie, Université de Limoges, Limoges, France.
authors: Marie-Odile
authors: MO
authors: Jauberteau
authors: Laboratoire Inflammation, Tissus Epithéliaux et Cytokines (LITEC-EA 4331), Université de Poitiers, Poitiers, France; Service Immunologie et inflammation, CHU de Poitiers, Poitiers, France.
authors: Jean-Claude
authors: JC
authors: Lecron
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D015870:Gene Expression; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053710:Interleukin-10 Receptor beta Subunit / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D014411:Neoplastic Stem Cells; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D000097043:Interleukin-22
chemical_list: D053710:Interleukin-10 Receptor beta Subunit; D007378:Interleukins; D051057:Proto-Oncogene Proteins c-akt; D018123:Receptors, Interleukin; D050796:STAT3 Transcription Factor; D000097043:Interleukin-22; C081846:IL10RB protein, human; C415369:interleukin-22 receptor