Date: Sunday, November 8, 2015
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Corticotropin releasing hormone (CRH) is the principal regulator of hypothalamus pituitary adrenal (HPA) axis. CRH and urocortin1 (UCN1) are member of the CRH family. These biological actions are mediated via CRH type1 receptor (CRHR1) and CRH type2 receptor (CRHR2). CRH and UCN1 are expressed in the cells of the immune system. We previously reported that CRH closely connected with the pathogenesis of RA. However, the function of CRH and UCN1 are poorly understood in autoimmune disease. On the other hand, recently, it was reported that IL-21 plays an important role on Sjogren’s syndrome (SS). The aim of this study is to reveal the biological function of CRH and UCN1 inducing IL-21 in SS.
We investigated the expression of CRH, UCN1, CRHR1 and CRHR2 by immunohistochemistry (IHC) and reverse transcription with the polymerase chain reaction (RT-PCR) in the salivary gland of patients with SS. We analyzed the function of CRH and UCN1 by NS-SV-DC cell lines, which are immortalized normal salivary gland ductal cells established by transfection with SV40. We examined the mRNA expression of CRH, UCN1, CRHR1, and CRHR2 in NS-SV-DC cell lines by RT-PCR. NS-SV-DC cell lines were cultured in the absence or presence of CRH (10-100nM) or UCN1 (10-100nM). After 24h of culture,IL-21 and IL-23 levels were measured by Enzyme-linked immune Sorbent assay (ELISA). We examined the mRNA expression of IL-21, IL-21 receptor, IL-23α and IL-23 receptor in NS-SV-DC stimulated by CRH or UCN1.
We detected the expression of mRNA and the protein level of CRH, UCN1 and CRHR2 in the SS patient`s salivary gland by RT-PCR and IHC staining. Moreover we found the mRNA expression of CRH, UCN1 and CRHR2 in NS-SV-DC by RT-PCR. The culture supernatants stimulated by CRH or UCN1 in NS-SV-DC cell lines showed that IL-21 and IL-23 levels increased in a dose-dependent manner by ELISA. To stimulate NS-SV-DC cell lines by CRH and UCN1, we investigated the increasing mRNA expression of IL-21 and IL-23α by RT-PCR.
The known function of IL-21 is facilitating differentiation, proliferation, survival of both B and T cells. IL-21 is elevated in the serum of patients with SS and is expressed by the lymphocytic infiltrating salivary gland. This is the first report that CRH and UCN1 were detected in salivary gland in patient with SS, and that CRH and UCN1 induce IL-21 and IL-23 production in NS-SV-DC cell lines. These results indicate that CRH or UCN1 play a crucial role of the IL-21 or IL-23 induction in salivary gland in pathogenesis of SS. Regulated IL-21 induction via CRH and UCN1 signal may be a novel therapeutic target in SS.
To cite this abstract in AMA style:Yokoyama Y, Matsui K, Kitano S, Furukawa T, Sekiguchi M, Azuma N, Kitano M, Tsunoda S, Iwasaki T, Sano H. The Novel Role of Corticotropin-Releasing Hormone and Urocortin1 on Sjogren’s Syndrome [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/the-novel-role-of-corticotropin-releasing-hormone-and-urocortin1-on-sjogrens-syndrome/. Accessed May 27, 2019.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-novel-role-of-corticotropin-releasing-hormone-and-urocortin1-on-sjogrens-syndrome/