Summary FcαR (CD89) plays important roles in immunoglobulin A (IgA)‐mediated immune responses. Soluble forms of FcαR (sFcαR) are found in the culture supernatants of FcαR‐expressing cells, in human serum and in the serum of FcαR transgenic mice, and have been suggested to be produced through a proteolytic process. However, little is known about the mechanism involved in the proteolytic release of sFcαR. In this study, we investigated the shedding mechanism of FcαR and determined the nature of the proteinase involved in FcαR shedding. In chemical inhibitor assays, shedding of FcαR was dramatically inhibited by EDTA, EGTA and a broad‐spectrum metalloproteinase inhibitor, GM6001, suggesting that a metalloproteinase was responsible for FcαR shedding. Overexpression of dominant‐negative mutants of ADAM (a disintegrin and metalloproteinase) 10 and ADAM17 markedly inhibited the production of sFcαR. Finally, knockdown of both endogenous ADAM10 and endogenous ADAM17 inhibited FcαR shedding, demonstrating that ADAM10 and ADAM17 were involved in the shedding of FcαR. The characterization of ADAM10 and ADAM17 as sFcαR‐releasing enzymes provides a novel insight into the molecular mechanism of sFcαR production and will help in further elucidation of the physiological and pathological roles of sFcαR.
Post-translational modifications on proteins are important in biological processes but may create neo-epitopes that induce autoimmune responses. In this study, we measured the serum IgG and IgM response to a set of non-modified or acetyl- and methyl-modified peptides corresponding to residues 1–19 of the histone 3 N-terminal tail in systemic lupus erythematosus (SLE) patients and healthy subjects. Our results indicated that the SLE patients and healthy subjects produced antibodies (Abs) to the peptides, but the two groups had different Ab isotype and epitope preferences. Abs to the non-modified form, H31–19, were of the IgG isotype and produced by SLE patients. They could not recognize the scrambled H31–19, which contained the same amino acid composition but a different sequence as H31–19. In comparison, healthy subjects in general did not produce IgG against H31–19. However, about 70% of the healthy subjects produced IgM Abs against mono-methylated K9 of H31–19 (H31–19K9me). Our further studies revealed that ε-amine mono-methylated lysine could completely inhibit the IgM binding to H31–19K9me, but lysine had no inhibitory effect. In addition, the IgM Abs could bind peptides containing a mono-methylated lysine residue but with totally different sequences. Thus, mono-methylated lysine was the sole epitope for the IgM. Interestingly, SLE patients had much lower levels of this type of IgM. There was no obvious correlation between the IgM levels and disease activity and the decreased IgM was unlikely caused by medical treatments.We also found that the IgM Abs were not polyreactive to dsDNA, ssDNA, lipopolysaccharide (LPS) or insulin and they did not exist in umbilical cord serum, implying that they were not natural Abs. The IgM Abs against mono-methylated lysine are present in healthy subjects but are significantly lower in SLE patients, suggesting a distinct origin of production and special physiological functions.
Objective. Primary dysmenorrhea (PD) is a common and high incidence disease in gynecology, which seriously affects the quality of life in young women. Our previous study found that mild moxibustion could treat abdominal pain of PD patients, but the mechanism is still unclear. Therefore, this study aims to partly investigate the treatment mechanism of moxibustion for PD, especially on uterine microcirculation. Methods. Forty 3-month-old Sprague Dawley female rats were randomly divided into four groups, including group A (saline control group, n = 10), group B (control plus moxibustion group, n = 10), group C (PD model group, n = 10), group D (PD. model plus moxibustion group, n = 10). The PD rat model was established by injecting estradiol benzoate and oxytocin. Mild moxibustion on Sanyinjiao (SP6) and Guanyuan (CV4) acupoints was once a day, 20 minutes per time, for 10 consecutive days. A vaginal smear was used to test the estrous cycle of rats. Uterine microvascular thickness was observed by stereomicroscope. And we detected the content of prostaglandin F2α (PGF2α) and prostaglandin E2 (PGE2) in uterine tissue by enzyme-linked immunosorbent assay. Results. Mild moxibustion can enlarge the microvessels, improve the microcirculation disturbance, and relieve the swelling of the uterus in PD rats. During the mild moxibustion intervention, the contents of PGF2α and PGE2 in uterus issues were synchronous increases or decreases and the changes of PGE2 were more obvious, but the changes of uterine microvasculature and morphology caused by the decrease of PGF2α were greater than PGE2. Conclusion. Mild moxibustion at SP6 and CV4 acupoints may relax uterine microvascular obstacle by reducing the content of PGF2α in uterine tissue, improve the microcirculation disorder, and then alleviate the PD rat’s uterine swelling.
Background and Aim: We aim to investigate the effects and mechanisms of electroacupuncture (EA) at ST25 and ST37 on the intestinal low-grade inflammation (LGI) in rat model of Diarrhea-predominant irritable bowel syndrome (IBS-D). Methods: IBS-D model rats were established by acetic acid enema combined with restraint and tail clamping. Before EA intervention, they were divided into three groups: blank 1 group, blank 2 group, and IBS-D model group. Diarrhea symptoms and visceral pain sensitivity were evaluated. After constructed the model successfully, the remaining IBS-D model group rats were randomly divided into model group and EA group. Local intestinal inflammation (HE staining), changes of intestinal mucosa (occludin protein and microvascular diameter) were evaluated. Differences between two groups were compared using t-test or Mann-Whitney U-test. Differences among more than two groups were compared using one-way ANOVA or Kruskal-Wallis test. Results: After modeling, the results of HE staining in intestinal tract of IBS-D model rats showed LGI. Compared with the model group, 4 h fecal moisture content (diarrhea index) and the AWR score were decreased in the EA group. The results of HE in EA group showed that the infiltration of intestinal inflammatory cells were alleviated. Additionally, EA significantly upregulated the expression of occludin protein and partially dilated the intestinal microvascular diameter. Pearson correlation analysis showed that the symptoms of IBS-D rats were correlated with the changes of intestinal mucosa. Conclusion: EA may treat intestinal LGI in IBS-D rats by upregulating the expression of occludin protein and dilating the intestinal microvascular diameter.Yu, and Sha Yang designed the experiment scheme. Sha Yang revised the manuscript. All authors have read and approved the publication of the final manuscript.
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