國家衛生研究院 NHRI:Item 3990099045/6718

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Title:	Identification of MCP-1 as a key effector of IL-31 signaling in Primary Cutaneous Amyloidosis
Authors:	Shiao, Y;Chung, H;Chiang, K;Chang, Y;Lee, D;Chen, C;Lin, M;Tsai, S;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 recently identified missense mutations from patients with familial PCA (FPCA) in either of the two subunits of the receptor for interleukin-31 (IL-31). To investigate the significance of the disease-derived mutation, we reconstituted in HaCaT human keratinocyte cell line a functional IL-31 receptor by exogenously expressing IL-31RA or an FPCA-derived mutant, IL-31RAS521F. Monocyte chemotactic protein-1 (MCP-1) was induced in the wild-type cells with IL-31 stimulation. This induction, however, was abrogated in mutant cells. MCP-1 is a secreted chemokine that can recruit innate immune cells to keratinocytes to scavenge cellular debris. In chemotaxis assay, monocytes were attracted to conditioned medium from IL-31-treated wild-type cells but not to that from the mutant cells. MCP-1 is the major chemoattractant in the conditioned medium as the chemoattraction ability is neutralized by MCP-1 antibody. In agreement with these in vitro observations, immunostaining of PCA skin samples showed much reduced level of MCP-1 compared to other skin condition samples. At the molecular level, the FPCA mutation attenuates STAT3 activation. STAT3 is an important factor to regulate MCP-1 expression as STAT3 knockdown by siRNA attenuated its expression. Thus, the diminished MCP-1 expression with the IL-31RA mutant is attributed, at least in part, to the reduced STAT3 activation. Taken together, our study suggests deficiency of immune cell chemoattraction by keratinocytes due to compromised MCP-1 production resulted from the IL-31RA mutation may play a role in FPCA pathogenesis.
Date:	2012-09
Relation:	Journal of Investigative Dermatology. 2012 Sep;132(Suppl. 2):S91.
Link to:	http://dx.doi.org/10.1038/jid.2012.302
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0022-202X&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000307814000514
Appears in Collections:	[Isao Matsuura] Conference Papers/Meeting Abstract [Shih-Feng Tsai] Conference Papers/Meeting Abstract

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