| 論文名 |
Activation of histamine H4 receptor inhibits TNFα/IMD-0354-induced apoptosis in human salivary NS-SV-AC cells. |
| 著者 |
Vasili Stegajev
Vesa-Petteri Kouri
Abdelhakim Salem
Stanislav Rozov
Holger Stark
Dan C E Nordstr?m
Yrj? T Konttinen
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| キーワード |
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| 出版年月 |
1970年1月 |
| 発表先 |
Apoptosis. 2014 Dec;19(12):1702-11. doi: 10.1007/s10495-014-1036-6. |
| WEBサイト |
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| 論文概要（和文） |
ヒスタミンH4受容体の活性化は、ヒト唾液NS-SV-AC細胞におけるTNFα/ IMD-0354誘発アポトーシスを阻害します |
| 論文概要（英文） |
Apoptosis is involved in the pathogenesis of Sj?gren's syndrome (SS), an autoimmune disease affecting exocrine glands. Our recent studies revealed diminished histamine H4 receptor (H?R) expression and impaired histamine transport in the salivary gland epithelial cells in SS. The aim was now to test if nanomolar histamine and high-affinity H?R signaling affect apoptosis of human salivary gland epithelial cell. Simian virus 40-immortalized acinar NS-SV-AC cells were cultured in serum-free keratinocyte medium ± histamine H?R agonist HST-10. Expression and internalization of H?R were studied by immunofluorescence staining ± clathrin inhibitor methyl-β-cyclodextrin (MβCD). Apoptosis induced using tumor necrosis factor-α with nuclear factor-κB inhibitor IMD-0354 was studied using phase contrast microscopy, Western blot, flow cytometry and polymerase chain reaction (qRT-PCR). HST-10-stimulated H?R internalization was inhibited by MβCD. Western blotting revealed diminished phosphorylated c-Jun N-terminal kinase JNK, but unchanged levels of phosphorylated extracellular signal regulated kinase pERK1/2 in H?R-stimulated samples compared to controls. qRT-PCR showed up-regulated expression of anti-apoptotic B cell lymphoma-extra large/Bcl-xL mRNAs and proteins, whereas pro-apoptotic Bcl-2-associated X protein/BAX remained unchanged in H4R-stimulated samples. H?R stimulation diminished cleavage of PARP and flow cytometry showed significant dose-dependent inhibitory effect of H?R stimulation on apoptosis. As far as we know this is the first study showing inhibitory effect of H?R activation on apoptosis of human salivary gland cells. Diminished H?R-mediated activation may contribute to loss of immune tolerance in autoimmune diseases and in SS in particular. |
