BackgroundLow levels of serum vitamin D is associated with several lung diseases. The production and activation of matrix metalloproteinases (MMPs) may play an important role in the pathogenesis of emphysema. The aim of the current study therefore is to investigate if vitamin D modulates the expression and activation of MMP-2 and MMP-9 in human lung fibroblasts (HFL-1) cells.MethodsHFL-1 cells were cast into three-dimensional collagen gels and stimulated with or without interleukin-1β (IL-1β) in the presence or absence of 100 nM 25-hydroxyvitamin D (25(OH)D) or 1,25-dihydroxyvitamin D (1,25(OH)2D) for 48 hours. Trypsin was then added into the culture medium in order to activate MMPs. To investigate the activity of MMP-2 and MMP-9, gelatin zymography was performed. The expression of the tissue inhibitor of metalloproteinase (TIMP-1, TIMP-2) was measured by enzyme-linked immunosorbent assay. Expression of MMP-9 mRNA and TIMP-1, TIMP-2 mRNA was quantified by real time reverse transcription polymerase chain reaction.ResultsIL-1β significantly stimulated MMP-9 production and mRNA expression. Trypsin converted latent MMP-2 and MMP-9 into their active forms of MMP-2 (66 kDa) and MMP-9 (82 kDa) within 24 hours. This conversion was significantly inhibited by 25(OH)D (100 nM) and 1,25(OH)2D (100 nM). The expression of MMP-9 mRNA was also significantly inhibited by 25(OH)D and 1,25(OH)2D.ConclusionVitamin D, 25(OH)D, and 1,25(OH)2D play a role in regulating human lung fibroblast functions in wound repair and tissue remodeling through not only inhibiting IL-1β stimulated MMP-9 production and conversion to its active form but also inhibiting IL-1β inhibition on TIMP-1 and TIMP-2 production.

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Background/Aims: Stress has a role in the pathogenesis of functional dyspepsia (FD) and influences food intake in humans and animals. Prokinetic drugs have been used in FD, and some of these drugs reverse the feeding inhibition (FI) induced by acute restraint stress in rats. We aimed to evaluate the effect of DA-9701 on FI induced by acute restraint in rats. Materials and Methods: Male Sprague-Dawley rats were divided into 6 groups: Control (no stress), Stress+vehicle, and Stress+DA-9701 at doses of 1, 3, 10, and 30 mg/kg (n=6∼7). DA-9701 or vehicle was administered through gastric gavage 45 minutes before stress. After 60 minutes of stress, pre-weighed chow was given and the weight of remaining food was measured 30 and 60 minutes later. The effect of DA-9701 on FI was compared after pretreatment with WAY100635, a 5HT1A antagonist. Results: The restraint stress group had significantly less food intake than the control group. After feeding, rats given 1 and 3 mg/kg of DA-9701 showed increased food intake at 60 minutes, but this was not statistically significant. Rats given 10 mg/kg of DA-9701 showed significantly increased food intake at 30 minutes and 60 minutes (P＜0.05). Interestingly, rats given 30 mg/kg of DA-9701 showed a significant decrease in food intake, similar to that of the vehicle group. The beneficial effect of 10 mg/kg of DA-9701 on FI was abolished by the pretreatment with WAY100635. Conclusions: Acute restraint stress reduced food intake in rats and pretreatment with DA-9701 improved stress-induced FI.(Korean J Helicobacter Up Gastrointest Res 2018;18:50-55)

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