title: Generation of bleomycin-induced lung fibrosis is independent of IL-16.
abstract: Given that CD4+ cells are found in the lungs of patients with fibrotic lung diseases such as idiopathic pulmonary fibrosis (IPF) we hypothesized that IL-16, a potent chemoattractant for CD4+ cells, may be involved in the pathogenesis of this disease. We found that baseline IL-16 gene expression is greater in fibroblasts isolated from IPF patients compared to non-fibrotic fibroblasts. Furthermore, IL-16 gene expression increased in IPF fibroblasts following stimulation with either of the pro-fibrotic growth factors TGFb1 or PDGF. In contrast, PDGF had no effect on IL-16 gene expression in non-fibrotic lung fibroblasts, whereas TGFb1 down-regulated IL-16 gene expression in non-fibrotic fibroblasts. To gain a better understanding of an association of IL-16 with fibrosis, we used the bleomycin-induced mouse model of fibrosis to examine IL-16 gene expression. Our current study demonstrates that IL-16, and its activator caspase 3, are highly expressed at the mRNA level in the lungs of mice prior to the deposition of collagen following intratracheal bleomycin administration. We then sought to determine the role of IL-16 in the generation of fibrosis in the mouse by using IL-16KO mice. There were no differences observed between IL-16WT and IL-16KO mice (cellular infiltrate, collagen deposition, total lung collagen generation and cytokine expression) following bleomycin instillation. These results indicate that IL-16 is prominently expressed in both murine and human fibrosis however as complete loss of this cytokine did not modulate pulmonary fibrosis, IL-16 is a candidate biomarker for IPF.
authors.affiliation: Discovery Research, Centocor R&D, 145 King of Prussia Road, Radnor, PA 19087, USA. wglass@cntus.jnj.com
authors.forename: William G
authors.initials: WG
authors.lastname: Glass
authors.forename: Rochelle L
authors.initials: RL
authors.lastname: Argentieri
authors.forename: Michelle
authors.initials: M
authors.lastname: Bracht
authors.forename: Francis X
authors.initials: FX
authors.lastname: Farrell
authors.forename: Anuk M
authors.initials: AM
authors.lastname: Das
authors.forename: Alfred M
authors.initials: AM
authors.lastname: Del Vecchio
authors.forename: Cory M
authors.initials: CM
authors.lastname: Hogaboam
authors.forename: Lynne A
authors.initials: LA
authors.lastname: Murray
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001761:Bleomycin / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis / Q000378:metabolism; D005434:Flow Cytometry / Q000379:methods; D019410:Interleukin-16 / Q000378:metabolism / Q000502:physiology*; D008168:Lung / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological
chemical_list: D000903:Antibiotics, Antineoplastic; D016207:Cytokines; D019410:Interleukin-16; D001761:Bleomycin; D003094:Collagen