کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6096909 | 1209877 | 2008 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Ae2a,b-Deficient Mice Develop Antimitochondrial Antibodies and Other Features Resembling Primary Biliary Cirrhosis
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کلمات کلیدی
TregPDC-E2HAlPQ-TOF/MSPBCAE2PHIFACSIntracellular pH - PH درون سلولیantimitochondrial antibodies - آنتی بادی ضد میکروبیAMA - اماinterleukin - اینترلوکینRegulatory T cells - سلولهای تی تنظیمکنندهPrimary biliary cirrhosis - سیروز صفراوی اولیهfluorescence-activated cell sorter - فلورسانس فعال سلول مرتب سازpolymerase chain reaction - واکنش زنجیره ای پلیمرازPCR - واکنش زنجیرهٔ پلیمراز
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
بیماریهای گوارشی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Background & Aims: Clâ/HCO3â anion exchanger 2 (AE2) is involved in intracellular pH (pHi) regulation and transepithelial acid-base transport, including secretin-stimulated biliary bicarbonate excretion. AE2 gene expression was found to be reduced in liver biopsy specimens and blood mononuclear cells from patients with primary biliary cirrhosis (PBC), a disease characterized by chronic nonsuppurative cholangitis associated with antimitochondrial antibodies (AMA) and other autoimmune phenomena. In mice with widespread Ae2 gene disruption, we previously reported altered spermiogenesis and reduced gastric acid secretion. We now describe the hepatobiliary and immunologic changes observed in these Ae2a.b-deficient mice. Methods: In this murine model, splenocyte pHi and T-cell populations were studied by flow cytometry. CD3-stimulated cytokine secretion was estimated using cytokine arrays. AMA were evaluated by immunoblotting and proteomics. Hepatobiliary changes were assessed by immunohistopathology, flow cytometry, and serum biochemistry. Cholangiocyte gene expression was analyzed by real-time polymerase chain reaction. Results:Ae2a,bâ/â mice exhibit splenomegaly, elevated pHi in splenocytes, increased production of interleukin-12p70 and interferon gamma, expanded CD8+ T-cell population, and under represented CD4+FoxP3+/regulatory T cells. Most Ae2a,bâ/â mice tested positively for AMA, showing increased serum levels of immunoglobulin M and G, and liver-specific alkaline phosphatase. About one third of Ae2a,bâ/â mice had extensive portal inflammation with CD8+ and CD4+ T lymphocytes surrounding damaged bile ducts. Cholangiocytes isolated from Ae2a,bâ/â mice showed gene expression changes compatible with oxidative stress and increased antigen presentation. Conclusions: Ae2 deficiency alters pHi homeostasis in immunocytes and gene expression profile in cholangiocytes, leading to immunologic and hepatobiliary changes that resemble PBC.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gastroenterology - Volume 134, Issue 5, May 2008, Pages 1482-1493
Journal: Gastroenterology - Volume 134, Issue 5, May 2008, Pages 1482-1493
نویسندگان
January T. Salas, Jesús M. Banales, Sarai Sarvide, Sergio Recalde, Alex Ferrer, Iker Uriarte, Ronald P.J. Oude Elferink, Jesús Prieto, Juan F. Medina,