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Please use this identifier to cite or link to this item:
http://ir.nhri.org.tw/handle/3990099045/6934
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| Title: | Identification of MCP-1 as a key effector of IL-31 signaling in Familial Primary Cutaneous Amyloidosis |
| Authors: | Shiao, YM;Chung, HJ;Chen, CC;Chiang, KN;Chang, YT;Lee, DD;Lin, MW;Tsai, SF;Matsuura, I |
| Contributors: | Institute of Molecular and Genomic Medicine |
| Abstract: | Primary cutaneous amyloidosis (PCA) is an itchy skin disorder that is relatively common in South America and Southeast Asia. We have recently identified missense mutations from patients with familial PCA (FPCA) in either of the two subunits (OSMRβ, IL-31RA) of the receptor for interleukin-31 (IL-31). To investigate the significance of the disease-derived mutation, we reconstituted in a human keratinocyte cell line, HaCaT, a functional IL-31 receptor by exogenously expressing IL-31RA or an FPCA-derived mutant, IL-31RA-S521F. With IL-31 stimulation, monocyte chemotactic protein-1 (MCP-1) was induced in the IL-31 receptor reconstituted cells. This effect, however, was abrogated in the cells carrying the IL-31RA-S521F mutant sequence. MCP-1 is a secreted chemokine that can recruit innate immune cells to target cells to scavenge cellular debris. In chemotaxis assays, monocytes were attracted to conditioned medium from IL-31-treated cells with the wild type sequence but not with the mutant sequence. MCP-1 was the major chemoattractant in the conditioned medium, as the chemoattraction ability was neutralized by the MCP-1 antibody. In agreement with these findings from the in vitro studies, immunostaining of PCA skin samples showed much reduced level of MCP-1 compared to those of other inflammatory or proliferative skin conditions. At the molecular level, the FPCA mutation attenuated STAT3 activation. Furthermore, STAT3 knockdown by siRNA caused a reduction of MCP-1 expression. Taken together, our data indicate that the deficiency of immune cell chemoattraction by keratinocytes due to compromised MCP-1 production may play a role in FPCA pathogenesis. |
| Date: | 2013-02 |
| Relation: | Journal of Dermatological Science. 2013 Feb;69(2):e54. |
| Link to: | http://dx.doi.org/10.1016/j.jdermsci.2012.11.467 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0923-1811&DestApp=IC2JCR |
| Appears in Collections: | [松浦功] 會議論文/會議摘要
[蔡世峯] 會議論文/會議摘要
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| SDO0923181112008122.pdf | | 70Kb | Adobe PDF | 652 | View/Open |
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