Transforming growth factor-β and interleukin-1β stimulate interleukin-11 secretion in human colonic subepithelial myofibroblasts

Prostate inflammation (PI) is a clinical condition associated with infection and/or inflammation of the prostate. It is a common disease frequently associated to lower urinary tract (LUT) symptoms. The urethra is an understudied structure in the LUT and plays a fundamental role in the urinary cycle. Here, we proposed to evaluate the effect of PI on the urethra tissue. Male Sprague-Dawley rats were used, and PI was induced by formalin injection into the ventral lobes of the prostate. The pelvic urethra at the prostatic level was harvested for histological analysis, contraction (electrical field stimulation and phenylephrine), and relaxation (sodium nitroprusside/MK-571) experiments. Various gene targets [cytochrome c oxidase subunit 2, transforming growth factor-β1, interleukin-1β, hypoxia-inducible factor-1α, α1A-adrenoceptor, inositol 1,4,5-trisphosphate receptor type 1, voltage-gated Ca2+ channel subunit-α1D, neuronal nitric oxide synthase, soluble guanylyl cyclase, phosphodiesterase 5A, protein kinase CGMP-dependent 1, and multidrug resistance-associated protein 5 (MRP5; ATP-binding cassette subfamily C member 5)] were quantified, and cGMP levels were measured. No histological changes were detected, and functional assays revealed decreased contraction and increased relaxation of urethras from the PI group. The addition of MK-571 to functional assays increased urethral relaxation. Genes associated with inflammation were upregulated in urethras from the PI group, such as cytochrome oxidase c subunit 2, transforming growth factor-β1, interleukin-1β, and hypoxia-inducible factor-1α. We also found increased expression of L-type Ca2+ channels and the neuronal nitric oxide synthase enzyme and decreased expression of the MRP5 pump. Finally, cGMP production was enhanced in urethral tissue of PI animals. The results indicate that PI is associated with proinflammatory gene expression in the urethra without histologically evident inflammation and that PI produces a dysfunctional urethra and MRP5 pump downregulation, which results in cGMP accumulation inside the cell. These findings would help to better understand LUT dysfunctions associated with PI and the role of MRP pumps in the control of LUT function.

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Analysis of proteoglycan synthesis by retro-ocular tissue fibroblasts under the influence of interleukin 1β and transforming growth factor-β

Acta Endocrinologica ◽

10.1530/eje.0.1310630 ◽

1994 ◽

Vol 131 (6) ◽

pp. 630-638 ◽

Cited By ~ 9

Author(s):

Yumi Imai ◽

Kyomi Ibaraki ◽

Ritsuko Odajima ◽

Yoshimasa Shishiba

Keyword(s):

Growth Factor ◽

Transforming Growth Factor ◽

Core Protein ◽

Transforming Growth Factor Β ◽

Interleukin 1Β ◽

Chain Elongation ◽

Ocular Tissue ◽

Proteoglycan Synthesis ◽

Core Proteins ◽

Sulfate Incorporation

Imai Y, Ibaraki K, Odajima R, Shishiba Y. Analysis of proteoglycan synthesis by retro-ocular tissue fibroblasts under the influence of interleukin 1β and transforming growth factor-β Eur J Endocrinol 1994;131:630–8. ISSN 0804–4643 Retro-ocular tissue fibroblasts are supposed to be responsible for the deposition of glycosaminoglycan in Graves' ophthalmopathy. We have reported in a preliminary fashion that interleukin 1β (IL-1β) and transforming growth factor-β (TGF-β) increased the rate of [35S]sulfate incorporation into proteoglycans two to five times the control in culture of retro-ocular tissue fibroblasts. The increase in the rate of [ S]sulfate incorporation into proteoglycan will occur as a result of: (a) net increase of proteoglycan synthesis; (b) elongation of glycosaminoglycan chains; (c) increased number of glycosaminoglycan chains; (d) oversulfation of glycosaminoglycan chains; (e) increase in cell number; (f) decreased rate of degradation. We have analyzed which mechanism is important for the increase of [35S]sulfate into proteoglycans observed in human retro-ocular tissue fibroblasts under the influence of cytokines. The last two possibilities (e, f) were ruled out because during the observation period there was no consistent proliferation of the cells and no decrease in the rate of degradation of proteoglycan examined by pulse-chase experiment. Cytokines did not change the size of glycosaminoglycan chains released from proteoglycan as measured by alkaline borohydride treatment, ruling out (b). Disaccharide analysis by HPLC after chondroitin sulfate ABC digestion revealed that glycosaminoglycan mainly contains monosulfated chondroitin disaccharides and that oversulfation was not observed under the influence of IL-1β or TGF-β, ruling out (d). The capacity to synthesize glycosaminoglycan chain in the presence of an artifical acceptor of chain elongation, β-d-xylodide, was increased significantly by IL-1β but not obviously so by TGF-β. Thus, an increased number of glycosaminoglycan chains (c) is possible for IL-1β. A preliminary northern blot analysis employing probes for mRNAs for various proteoglycan core proteins showed increased expression of versican and aggrecan in the presence of IL-1β or TGF-β. This result supports the possibility of (a). In conclusion, IL-1β and TGF-β increased [35S]sulfate incorporation into proteoglycan by increasing the net increase of proteoglycan synthesis and possibly by increasing the number of glycosaminoglycan chains attached to core protein in the case of IL-1β. Y Shishiba, Division of Endocrinology, Department of Medicine, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, Japan

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