کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5918095 | 1163826 | 2009 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The adenylyl cyclase-cAMP system suppresses TARC/CCL17 and MDC/CCL22 production through p38 MAPK and NF-κB in HaCaT keratinocytes
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شناسی مولکولی
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چکیده انگلیسی
Patients with atopic dermatitis (AD) have significantly reduced plasma cAMP levels, and the cAMP level is correlated with the immunopathogenesis of AD. The production of thymus and activation-regulated chemokine (TARC/CCL17) and macrophage-derived chemokine (MDC/CCL22) in keratinocytes is significantly enhanced in patients with AD. In the present study, we investigated the in vitro effects of the adenylyl cyclase-cAMP system on IFN-γ and TNF-α-stimulated production of TARC and MDC in human HaCaT keratinocytes. Both forskolin (a direct activator of adenylyl cyclase) and dibutyryl-cAMP (DBcAMP, a permeable analog of cAMP) suppressed production of TARC and MDC in parallel with the activation of NF-κB in IFN-γ and TNF-α-stimulated HaCaT cells. Moreover, inhibition of NF-κB suppressed TARC and MDC production induced by IFN-γ plus TNF-α. However, dideoxyforskolin, a forskolin derivative that does not activate cAMP, failed to suppress the secretion of these chemokines. An inhibitor of p38 MAPK suppressed the production of TARC and MDC in parallel to the activation of NF-κB in HaCaT cells. Of note, the IFN-γ plus TNF-α-stimulated activation of p38 MAPK was suppressed following incubation with forskolin or DBcAMP alone. These results indicate that the adenylyl cyclase-cAMP system has an inhibitory role in IFN-γ plus TNF-α-stimulated production of TARC and MDC in HaCaT keratinocytes by inhibiting NF-κB activation through p38 MAPK pathway, implying that the adenylyl cyclase-cAMP system could be a candidate therapeutic target of Th2-skewed skin inflammation such as AD.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Immunology - Volume 46, Issue 10, June 2009, Pages 1925-1934
Journal: Molecular Immunology - Volume 46, Issue 10, June 2009, Pages 1925-1934
نویسندگان
Xu-Feng Qi, Dong-Heui Kim, Yang-Suk Yoon, Jian-Hong Li, Soon-Bong Song, Dan Jin, Xue-Zhu Huang, Yung-Chien Teng, Kyu-Jae Lee,