title: Tumor necrosis factor-stimulated gene-6 (TSG-6) amplifies hyaluronan synthesis by airway smooth muscle cells.
abstract: We tested the hypothesis that the artificial addition of heavy chains from inter-α-inhibitor to hyaluronan (HA), by adding recombinant TSG-6 (TNF-stimulated gene-6) to the culture medium of murine airway smooth muscle (MASM) cells, would enhance leukocyte binding to HA cables produced in response to poly(I:C). As predicted, the addition of heavy chains to HA cables enhanced leukocyte adhesion to these cables, but it also had several unexpected effects. (i) It produced thicker, more pronounced HA cables. (ii) It increased the accumulation of HA in the cell-associated matrix. (iii) It decreased the amount of HA in the conditioned medium. Importantly, these effects were observed only when TSG-6 was administered in the presence of poly(I:C), and TSG-6 did not exert any effect on its own. Increased HA synthesis occurred during active, poly(I:C)-induced HA synthesis and did not occur when TSG-6 was added after poly(I:C)-induced HA synthesis was complete. MASM cells derived from TSG-6(-/-), HAS1/3(-/-), and CD44(-/-) mice amplified HA synthesis in response to poly(I:C) + TSG-6 in a manner similar to WT MASM cells, demonstrating that they are expendable in this process. We conclude that TSG-6 increases the accumulation of HA in the cell-associated matrix, partially by preventing its dissolution from the cell-associated matrix into the conditioned medium, but primarily by inducing HA synthesis.
authors.affiliation: Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio 44195, USA. lauerm1@ccf.org
authors.forename: Mark E
authors.initials: ME
authors.lastname: Lauer
authors.forename: Georgiana
authors.initials: G
authors.lastname: Cheng
authors.forename: Shadi
authors.initials: S
authors.lastname: Swaidani
authors.forename: Mark A
authors.initials: MA
authors.lastname: Aronica
authors.forename: Paul H
authors.initials: PH
authors.lastname: Weigel
authors.forename: Vincent C
authors.initials: VC
authors.lastname: Hascall
mesh_terms: D000818:Animals; D002241:Carbohydrates / Q000737:chemistry; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism; D005456:Fluorescent Dyes / Q000494:pharmacology; D006720:Homozygote; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry / Q000378:metabolism*; D007249:Inflammation; D007962:Leukocytes / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D011070:Poly I-C / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism*; D014132:Trachea / Q000378:metabolism; D020298:U937 Cells
chemical_list: D002241:Carbohydrates; D015815:Cell Adhesion Molecules; D017077:Culture Media, Conditioned; D005456:Fluorescent Dyes; D011994:Recombinant Proteins; C513057:Tnfaip6 protein, mouse; D006820:Hyaluronic Acid; D011070:Poly I-C