title: IL-4 and IL-13 specifically increase adhesion molecule and inflammatory cytokine expression in human lung fibroblasts.
abstract: Subepithelial fibrosis in the bronchi of asthmatics is the result of an irreversible lung fibroblast activation, triggered by cytokines secreted by IL-4- and IL-5-activated inflammatory cells. Here, we provide evidence that human lung fibroblasts (ICIG7 cells) express a single class of high-affinity IL-4 receptor (IL-4R). This receptor is functional and composed of at least the IL-4Ralpha and IL-13Ralpha1 chains in the absence of the IL-2Rgamma chain. The IL-4Ralpha is efficiently internalized at 37 degrees C within 15 min in the presence of IL-4, whereas this process is slower with IL-13. In ICIG7 cells, IL-4 triggers the tyrosine phosphorylation of at least two proteins (110 and 180 kDa), and up-regulates the transcription of c-fos, c-jun and c-myc proto-oncogenes. In addition, the secretion of several cytokines [IL-6, granulocyte colony stimulating factor and granulocyte macrophage colony stimulating factor (GM-CSF)] as well as the expression of beta1 integrin and VCAM-1 adhesion molecules are augmented by IL-4. IL-13 displays similar biological activities, but less effectively than IL-4. On the other hand, ICIG7 cells could constitute a lung fibroblast population defined by the spontaneous release of several pro-inflammatory cytokines (IL-6, IL-11 and GM-CSF) and cell surface phenotype (CD4 and Thy-1). Through this peculiar cytokine pattern and the IL-4/IL-13-dependent activities, these cells could act as effector cells in the pathogenesis of asthma, triggering and maintaining the recruitment, homing and activation of bone marrow-derived inflammatory cells, and playing a role in the remodeling process of the airways.
authors.affiliation: U268 INSERM Hôpital Paul Brousse, Villejuif, France.
authors.forename: C
authors.initials: C
authors.lastname: Doucet
authors.forename: D
authors.initials: D
authors.lastname: Brouty-Boyé
authors.forename: C
authors.initials: C
authors.lastname: Pottin-Clemenceau
authors.forename: C
authors.initials: C
authors.lastname: Jasmin
authors.forename: G W
authors.initials: GW
authors.lastname: Canonica
authors.forename: B
authors.initials: B
authors.lastname: Azzarone
mesh_terms: D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002478:Cells, Cultured / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000096:biosynthesis; D018793:Interleukin-13 / Q000378:metabolism / Q000494:pharmacology*; D053661:Interleukin-13 Receptor alpha1 Subunit; D015847:Interleukin-4 / Q000378:metabolism / Q000494:pharmacology*; D015850:Interleukin-6 / Q000235:genetics; D007457:Iodine Radioisotopes / Q000378:metabolism; D010766:Phosphorylation; D011014:Pneumonia / Q000378:metabolism* / Q000473:pathology*; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines; C508181:IL13RA1 protein, human; D019012:Integrin beta1; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D015850:Interleukin-6; D007457:Iodine Radioisotopes; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4; D019010:Vascular Cell Adhesion Molecule-1; D015847:Interleukin-4; D011505:Protein-Tyrosine Kinases