OBJECTIVE Although it is generally believed that nicotine accounts for the beneficial effect of smoking on ulcerative colitis,the underlying mechanisms remain not well-understood.Our previous finding that nicotine inh...OBJECTIVE Although it is generally believed that nicotine accounts for the beneficial effect of smoking on ulcerative colitis,the underlying mechanisms remain not well-understood.Our previous finding that nicotine inhibits inflammatory responses through inducing miRNA-124 prompted us to ask whether the miRNA is involved in the protective action of nicotine on UC.METHODS Mi R-124 expression in colon tissues and cells was determined by q-PCR and in situ hybridization.The effect of miR-124 on protective role of nicotine in ulcerative colitis was evaluated in DSS-treated mice and IL-6-treated Caco-2 colon epithelial cells.Expression of p-STAT3/STAT3 was detected by immunohistochemistry and Western blot analysis.RESULTS miR-124 expression is upregulated in colon tissues from patients and DSS-induced colitis.Nicotine treatment further elevated miR-124 level in colon tissues of the mice,in infiltrated lymphocytes and epithelial cells,and augmented miR-124 expression in lymphocytes isolated from human ulcerative colon tissues.Administration of nicotine also reduced weight loss,improved DAI and decreased HE score in DSS-induced colitis.Moreover,knockdown of miR-124 in vivo significantly diminished the beneficial effect of nicotine,and in vitro on IL-6-treated Caco-2 colon epithelial cells.Further analysis indicated that nicotine inhibited STAT3 activation in vivo and in IL-6-treated Caco-2 colon epithelial cells and Jurkat human T lymphocytes,in whichmiR-124 knockdown led to increased activation of STAT3.CONCLUSION These data indicated that nicotine exerts its protective action in UC through inducing miR-124 and its effect on STAT3,suggesting that the miR-124/STAT3 system is a potential target for the therapeutic intervention of UC.展开更多
A large body of epidemiological and clinical evidences indicated that smoking has a protective effect in patients with ulcerative colitis （UC）. Although it is generally believed that nicotine accounts for the benefi...A large body of epidemiological and clinical evidences indicated that smoking has a protective effect in patients with ulcerative colitis （UC）. Although it is generally believed that nicotine accounts for the beneficial effect of smoking on UC, the underlying mechanism remains largely unknown. Our previously investigations demon- strated that nicotine inhibits inflammatory responses via inducing miRNA-124, which prompted us to ask whether miR-124 is involved in the protective effect of nicotine on UC. We found in the present study that nicotine elevated the level of miR-124 in epithelial colon cancer cell HT-29. MiR-124 overexpression decreased LPS-triggered STAT3 phosphorylation and STAT3 upregulation, whereas its knockdown enhanced LPS-induced p-STAT3/STAT3 increase. In mice UC model, nicotine treatment reduced weight loss, improved disease activity index, decreased HE score and increased miR-124 expression in colon tissues. Furthermore, miR-124 knockdown markedly dimin- ished the beneficial effect of nicotine in UC mice, and attenuated the inhibitory role of nicotine on the STAT3 /p- STAT3 expression in colon tissues. Consistent with its involvement in UC, biopsies samples from patients with UC also contained increased level of miR-124 when compared with that from normal individuals. These data showed that miR-124 is involved in UC and mediates the protective effects of nicotine, suggesting that the mitl-124/STAT3 is a potential target for the therapeutic intervention of UC.展开更多
OBJECTIVE Although it is generally believed that nicotine accounts for the beneficial effect of smoking on ulcerative colitis,the underlying mechanisms remain not well understood.Our previous finding that nicotine inh...OBJECTIVE Although it is generally believed that nicotine accounts for the beneficial effect of smoking on ulcerative colitis,the underlying mechanisms remain not well understood.Our previous finding that nicotine inhibits inflammatory responses through inducing miRNA-124 prompted us to ask whether the miRNA is involved in the protective action of nicotine on UC.METHODS MiR-124 expres.sion in colon tissues and cells was determined by q-PCR and in situ hybridization.The effect of miR-124 on protective role of nicotine in ulcerative colitis was evaluated in DSS-treated mice and IL-6-treated Caco-2 colon epithelial cells.Expression of p-STAT3/STAT3 was detected by immunohistochemistry and Western-blot analysis.RESULTS miR-124 expression is upregulated in colon tissues from UC patients and DSS-induced colitis mice.Nicotine treatment further elevated miR-124 level in lympho.cytes isolated from human ulcerative colonic mucosa and ulcerative colon tissues from DSS mice,both in infiltrated lymphocytes and epithelial cells.Administration of nicotine also reduced weight loss,improved DAI and decreased HE score in DSS-induced colitis mice.Moreover,knockdown of miR-124 in vivo significantly diminished the beneficial effect of nicotine on murine colitis,and in vitro on IL-6-treated Caco-2 colon epithelial cells.Further analysis indicated that nicotine inhibited STAT3 activation in vivo and in IL-6-treated Caco-2 colon epithelial cells and Jurkat human T lymphocytes,in which miR-124 knockdown led to increased activation of STAT3.Blocking STAT3 activity alone is beneficial for DSS colitis and also abolished nicotine′s protective effect in this model.CONCLUSION These data indicated that nicotine exerts its protective action in UC through inducing miR-124 and its effect on STAT3,and suggest that the miR-124/STAT3 system is a potential target for the therapeutic intervention of UC.展开更多
基金supported by National Natural Science Foundation of China(81273606,81473259 to XL,81603116 to YS)National Science and Technology Major Project(2014ZX09J14103-08C to XL)
文摘OBJECTIVE Although it is generally believed that nicotine accounts for the beneficial effect of smoking on ulcerative colitis,the underlying mechanisms remain not well-understood.Our previous finding that nicotine inhibits inflammatory responses through inducing miRNA-124 prompted us to ask whether the miRNA is involved in the protective action of nicotine on UC.METHODS Mi R-124 expression in colon tissues and cells was determined by q-PCR and in situ hybridization.The effect of miR-124 on protective role of nicotine in ulcerative colitis was evaluated in DSS-treated mice and IL-6-treated Caco-2 colon epithelial cells.Expression of p-STAT3/STAT3 was detected by immunohistochemistry and Western blot analysis.RESULTS miR-124 expression is upregulated in colon tissues from patients and DSS-induced colitis.Nicotine treatment further elevated miR-124 level in colon tissues of the mice,in infiltrated lymphocytes and epithelial cells,and augmented miR-124 expression in lymphocytes isolated from human ulcerative colon tissues.Administration of nicotine also reduced weight loss,improved DAI and decreased HE score in DSS-induced colitis.Moreover,knockdown of miR-124 in vivo significantly diminished the beneficial effect of nicotine,and in vitro on IL-6-treated Caco-2 colon epithelial cells.Further analysis indicated that nicotine inhibited STAT3 activation in vivo and in IL-6-treated Caco-2 colon epithelial cells and Jurkat human T lymphocytes,in whichmiR-124 knockdown led to increased activation of STAT3.CONCLUSION These data indicated that nicotine exerts its protective action in UC through inducing miR-124 and its effect on STAT3,suggesting that the miR-124/STAT3 system is a potential target for the therapeutic intervention of UC.
文摘A large body of epidemiological and clinical evidences indicated that smoking has a protective effect in patients with ulcerative colitis （UC）. Although it is generally believed that nicotine accounts for the beneficial effect of smoking on UC, the underlying mechanism remains largely unknown. Our previously investigations demon- strated that nicotine inhibits inflammatory responses via inducing miRNA-124, which prompted us to ask whether miR-124 is involved in the protective effect of nicotine on UC. We found in the present study that nicotine elevated the level of miR-124 in epithelial colon cancer cell HT-29. MiR-124 overexpression decreased LPS-triggered STAT3 phosphorylation and STAT3 upregulation, whereas its knockdown enhanced LPS-induced p-STAT3/STAT3 increase. In mice UC model, nicotine treatment reduced weight loss, improved disease activity index, decreased HE score and increased miR-124 expression in colon tissues. Furthermore, miR-124 knockdown markedly dimin- ished the beneficial effect of nicotine in UC mice, and attenuated the inhibitory role of nicotine on the STAT3 /p- STAT3 expression in colon tissues. Consistent with its involvement in UC, biopsies samples from patients with UC also contained increased level of miR-124 when compared with that from normal individuals. These data showed that miR-124 is involved in UC and mediates the protective effects of nicotine, suggesting that the mitl-124/STAT3 is a potential target for the therapeutic intervention of UC.
基金supported by National Natural Science Foundation of China(8147325981603116)
文摘OBJECTIVE Although it is generally believed that nicotine accounts for the beneficial effect of smoking on ulcerative colitis,the underlying mechanisms remain not well understood.Our previous finding that nicotine inhibits inflammatory responses through inducing miRNA-124 prompted us to ask whether the miRNA is involved in the protective action of nicotine on UC.METHODS MiR-124 expres.sion in colon tissues and cells was determined by q-PCR and in situ hybridization.The effect of miR-124 on protective role of nicotine in ulcerative colitis was evaluated in DSS-treated mice and IL-6-treated Caco-2 colon epithelial cells.Expression of p-STAT3/STAT3 was detected by immunohistochemistry and Western-blot analysis.RESULTS miR-124 expression is upregulated in colon tissues from UC patients and DSS-induced colitis mice.Nicotine treatment further elevated miR-124 level in lympho.cytes isolated from human ulcerative colonic mucosa and ulcerative colon tissues from DSS mice,both in infiltrated lymphocytes and epithelial cells.Administration of nicotine also reduced weight loss,improved DAI and decreased HE score in DSS-induced colitis mice.Moreover,knockdown of miR-124 in vivo significantly diminished the beneficial effect of nicotine on murine colitis,and in vitro on IL-6-treated Caco-2 colon epithelial cells.Further analysis indicated that nicotine inhibited STAT3 activation in vivo and in IL-6-treated Caco-2 colon epithelial cells and Jurkat human T lymphocytes,in which miR-124 knockdown led to increased activation of STAT3.Blocking STAT3 activity alone is beneficial for DSS colitis and also abolished nicotine′s protective effect in this model.CONCLUSION These data indicated that nicotine exerts its protective action in UC through inducing miR-124 and its effect on STAT3,and suggest that the miR-124/STAT3 system is a potential target for the therapeutic intervention of UC.
