MIA： Human β-defensin （HBD）-1 and HBD-2 are endogenous antimicrobial peptides. Unlike HBD-1, the HBD-2 expression is augmented by Helicobacter pylori （H pylon）. We sought to determine HBD-1 and HBD-2 concentrati...MIA： Human β-defensin （HBD）-1 and HBD-2 are endogenous antimicrobial peptides. Unlike HBD-1, the HBD-2 expression is augmented by Helicobacter pylori （H pylon）. We sought to determine HBD-1 and HBD-2 concentrations in gastric juice during Hpylori infection. METHODS： HBD-1 and HBD-2 concentrations were measured by radioimmunoassay in plasma and gastric juice of 49 Hpylori-infected and 33 uninfected subjects and before and after anti-H pyloritreatment in,13 patients with Hpylori-associated gastritis. Interleukin （IL）-1β and IL-8 concentrations in gastric juice were measured by enzyme-linked immunosorbent assay （ELISA）. Histological grades of gastritis were determined using two biopsy specimens taken from the antrum and corpus. Reverse phase high performance liquid chromatography （RP-HPLC） was used to identify HBD-2. RESULTS： HBD-2 concentrations in gastric juice, but not in plasma, were significantly higher in Hpylori-positive than -negative subjects, albeit the post-treatment levels were unchanged. Immunoreactivity for HBD-2 was exclusively identified in Hpylori-infected mucosa by RPHPLC. HBD-2 concentrations in gastric juice correlated with histological degree of neutrophil and mononuclear cell infiltration in the corpus. IL-1β levels correlated with those of IL-8, but not HBD-2. Plasma and gastric juice HBD-1 concentrations were similar in H pylori-infected and uninfected subjects. CONCLUSION： Our results place the β-defensins, especiallyHBD-2, in the front line of innate immune defence. Moreover, HBD-2 may be involved in the pathogenesis of Hpylori-associated gastritis, possibly through its function as immune and inflammatory mediator.展开更多
DICER1 is a key enzyme responsible for the maturation of microRNAs. Recent evidences suggested that DICER1 and microRNAs expressed in epididymis were involved in the control of male fertility. However, the exact mecha...DICER1 is a key enzyme responsible for the maturation of microRNAs. Recent evidences suggested that DICER1 and microRNAs expressed in epididymis were involved in the control of male fertility. However, the exact mechanism remains to be elucidated. Here, we created a mouse line by targeted disruption of Dicerl gene in the principal cells of distal caput epididymis. Our data indicated that a set of β-defensin genes were downregulated by DICER1 rather than by microRNAs. Moreover, DICER1 was significantly enriched in the promoter of β-defensin gene and controlled transcription. Besides, the antibacterial ability of the adult epididymis significantly declined upon Dicerl deletion both in vitro and in vivo. And a higher incidence of reproductive defect was observed in middle-aged Dicerl^-|- males. These results suggest that DICER1 plays an important role in transcription of β-defensin genes, which are associated with the natural antibacterial properties in a microRNA-independent manner, and further impacts the male fertility.展开更多
Anti-microbial peptides are essential for the intestinal innate immunity that protects the intestinal epithelia from attacks by foreign pathogens. Human β-defensin (HBD) is one of the pivotal anti-microbial peptides ...Anti-microbial peptides are essential for the intestinal innate immunity that protects the intestinal epithelia from attacks by foreign pathogens. Human β-defensin (HBD) is one of the pivotal anti-microbial peptides that are expressed in the colonic epithelia. This study investigated the effect and the signaling mechanism of inducible β-defensin HBD2 by an essential amino acid, isoleucine (Ile) in colonic epithelial cells. Here we examined the expression level of HBD2 on induction of Ile in epithelial cells, and checked this pathway. HBD2 mRNA was induced by co-incubation with IL-1α and Ile in Caco2 cells, but not by Ile alone. An inhibitor of either ERK or Gi, a subunit of G-proteins, reduced the induction of HBD2 mRNA by Ile. The treatment with Ile also increased the intracellular calcium ion concentration, thus suggesting that the GPCR and ERK signaling pathway mediate the effects of Ile. These results indicate that an essential amino acid, Ile, enhances the expression of an inducible β-defensin, namely HBD2, by IL-1α through the activation of GPCRs and ERK signaling pathway. The administration of Ile may therefore represent a possible option to safely treat intestinal inflammation.展开更多
文摘MIA： Human β-defensin （HBD）-1 and HBD-2 are endogenous antimicrobial peptides. Unlike HBD-1, the HBD-2 expression is augmented by Helicobacter pylori （H pylon）. We sought to determine HBD-1 and HBD-2 concentrations in gastric juice during Hpylori infection. METHODS： HBD-1 and HBD-2 concentrations were measured by radioimmunoassay in plasma and gastric juice of 49 Hpylori-infected and 33 uninfected subjects and before and after anti-H pyloritreatment in,13 patients with Hpylori-associated gastritis. Interleukin （IL）-1β and IL-8 concentrations in gastric juice were measured by enzyme-linked immunosorbent assay （ELISA）. Histological grades of gastritis were determined using two biopsy specimens taken from the antrum and corpus. Reverse phase high performance liquid chromatography （RP-HPLC） was used to identify HBD-2. RESULTS： HBD-2 concentrations in gastric juice, but not in plasma, were significantly higher in Hpylori-positive than -negative subjects, albeit the post-treatment levels were unchanged. Immunoreactivity for HBD-2 was exclusively identified in Hpylori-infected mucosa by RPHPLC. HBD-2 concentrations in gastric juice correlated with histological degree of neutrophil and mononuclear cell infiltration in the corpus. IL-1β levels correlated with those of IL-8, but not HBD-2. Plasma and gastric juice HBD-1 concentrations were similar in H pylori-infected and uninfected subjects. CONCLUSION： Our results place the β-defensins, especiallyHBD-2, in the front line of innate immune defence. Moreover, HBD-2 may be involved in the pathogenesis of Hpylori-associated gastritis, possibly through its function as immune and inflammatory mediator.
基金the National Basic Research Program of China(973 Program2014CB943103)the National Natural Science Foundation of China(31471104,31671203,and 31571192).
文摘DICER1 is a key enzyme responsible for the maturation of microRNAs. Recent evidences suggested that DICER1 and microRNAs expressed in epididymis were involved in the control of male fertility. However, the exact mechanism remains to be elucidated. Here, we created a mouse line by targeted disruption of Dicerl gene in the principal cells of distal caput epididymis. Our data indicated that a set of β-defensin genes were downregulated by DICER1 rather than by microRNAs. Moreover, DICER1 was significantly enriched in the promoter of β-defensin gene and controlled transcription. Besides, the antibacterial ability of the adult epididymis significantly declined upon Dicerl deletion both in vitro and in vivo. And a higher incidence of reproductive defect was observed in middle-aged Dicerl^-|- males. These results suggest that DICER1 plays an important role in transcription of β-defensin genes, which are associated with the natural antibacterial properties in a microRNA-independent manner, and further impacts the male fertility.
文摘Anti-microbial peptides are essential for the intestinal innate immunity that protects the intestinal epithelia from attacks by foreign pathogens. Human β-defensin (HBD) is one of the pivotal anti-microbial peptides that are expressed in the colonic epithelia. This study investigated the effect and the signaling mechanism of inducible β-defensin HBD2 by an essential amino acid, isoleucine (Ile) in colonic epithelial cells. Here we examined the expression level of HBD2 on induction of Ile in epithelial cells, and checked this pathway. HBD2 mRNA was induced by co-incubation with IL-1α and Ile in Caco2 cells, but not by Ile alone. An inhibitor of either ERK or Gi, a subunit of G-proteins, reduced the induction of HBD2 mRNA by Ile. The treatment with Ile also increased the intracellular calcium ion concentration, thus suggesting that the GPCR and ERK signaling pathway mediate the effects of Ile. These results indicate that an essential amino acid, Ile, enhances the expression of an inducible β-defensin, namely HBD2, by IL-1α through the activation of GPCRs and ERK signaling pathway. The administration of Ile may therefore represent a possible option to safely treat intestinal inflammation.
