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Interesting study about NO.
Excessive nitric oxide impairs wound collagen accumulation.
Julie E Park,
Morton J Abrams,
Philip A Efron,
Adrian Barbul
Department of Surgery, Sinai Hospital of Baltimore, Baltimore, Maryland; Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Journal of Surgical Research (Impact Factor: 2.02). 12/2012; DOI:10.1016/j.jss.2012.11.056 Source:
PubMed
ABSTRACT BACKGROUND: Nitric oxide (NO) plays a major regulatory role in wound collagen synthesis. We hypothesized that this regulatory role is tightly controlled by the levels of NO in the wound environment and that supranormal wound NO generation impairs wound collagen accumulation. MATERIALS AND METHODS: We used the model of turpentine-induced granuloma in male Sprague-Dawley rats as a sterile inflammatory stimulus generating large amounts of NO. In this environment, NO generation increased by 260%, whereas collagen deposition was significantly reduced by 38.5% (729.7 ± 81.5 versus 449.4 ± 76.3 μg hydroxyproline/100 mg sponge, P<0.05). Inhibition of NO synthase activity using 300 mM L-N6-(1-iminoethyl)-lysine, a highly potent and selective inhibitor of inducible NO synthase, significantly reduced NO elevation by 43.3% and increased wound collagen deposition by 37.3% (P<0.05). These effects occurred without any anti-inflammatory effects of L-N6-(1-iminoethyl)-lysine as assessed by the white blood cell counts and levels of interleukins 1 and 6. CONCLUSIONS:
The data show that high levels of NO within the wound environment significantly reduce wound collagen deposition. Inhibition of NO generation restores collagen levels to normal levels. The regulatory effects of NO on wound collagen appear to be highly correlated with the amount of NO generated.
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Nitric oxide inhibits androgen receptor-mediated collagen production in human gingival fibroblasts.
Lin SJ,
Lu HK,
Lee HW,
Chen YC,
Li CL,
Wang LF.
Source
Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan Periodontal Department, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.
Abstract
Lin S-J, Lu H-K, Lee H-W, Chen Y-C, Li C-L, Wang L-F. Nitric oxide inhibits androgen receptor-mediated collagen production in human gingival fibroblasts. J Periodont Res 2012; 47: 701-710. © 2012 John Wiley & Sons A/S Background and Objective:
In our previous study, we found that flutamide [an androgen receptor (AR) antagonist] inhibited the up-regulation of collagen induced by interleukin (IL)-1β and/or nifedipine in gingival fibroblasts. The present study attempted to verify the role of nitric oxide (NO) in the IL-1β/nifedipine-AR pathway in gingival overgrowth. Material and Methods: Confluent gingival fibroblasts derived from healthy individuals (n = 4) and those with dihydropyridine-induced gingival overgrowth (DIGO) (n = 6) were stimulated for 48 h with IL-1β (10 ng/mL), nifedipine (0.34 μm) or IL-1β + nifedipine. Gene and protein expression were analyzed with real-time RT-PCR and western blot analyses, respectively. Meanwhile, Sircol dye-binding and the Griess reagent were, respectively, used to detect the concentrations of total soluble collagen and nitrite in the medium. Results: IL-1β and nifedipine simultaneously up-regulated the expression of the AR and type-I collagen α1 [Colα1(I)] genes and the total collagen concentration in DIGO cells (p < 0.05). IL-1β strongly increased the expression of inducible nitric oxide synthase (iNOS) mRNA and the nitrite concentration in both healthy and DIGO cells (p < 0.05). However, co-administration of IL-1β and nifedipine largely abrogated the expression of iNOS mRNA and the nitrite concentration with the same treatment. Spearman's correlation coefficients revealed a positive correlation between the AR and total collagen (p < 0.001), but they both showed a negative correlation with iNOS expression and the NO concentration (p < 0.001). The iNOS inhibitor, 1400W, enhanced IL-1β-induced AR expression; furthermore, the NO donor, NONOate, diminished the expression of the AR to a similar extent in gingival fibroblasts derived from both healthy patients and DIGO patients (p < 0.05). Conclusion: IL-1β-induced NO attenuated AR-mediated collagen production in human gingival fibroblasts. The iNOS/NO system down-regulated the axis of AR/Colα1(I) mRNA expression and the production of AR/total collagen proteins by DIGO cells.