1. ¹Institute of Basic Medical Sciences, Medical College, National Cheng Kung University, Tainan, Taiwan
2. ²Department of Medical Technology, Chung Hwa University of Medical Technology, Tainan, Taiwan
3. ³Institute of Biopharmaceutical Sciences, Medical College, National Cheng Kung University, Tainan, Taiwan
4. ⁴Graduate Institute of Biochemistry and Molecular Biology, Medical College, National Cheng Kung University, Tainan, Taiwan
5. ⁵Department of Medical Research, Chi-Mei Medical Center, Tainan, Taiwan

Correspondence: M-S Chang, Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan. E-mail: mschang@mail.ncku.edu.tw

Received 22 April 2008; Revised 17 June 2008; Accepted 18 June 2008; Published online 4 September 2008.

Abstract

We identified a novel soluble protein, mouse (m)IL-20R1a, generated by alternative splicing of the mIL-20R1 gene, which encodes one subunit of the receptor complex for mIL-19, mIL-20 and mIL-24. mIL-20R1a has 77.14% amino-acid identity with the extracellular domain of mIL-20R1. However, no significant interaction between mIL-20R1a and mIL-19 or mIL-20 was detected. Consequently, we aimed to clarify whether mIL-20R1a might function as a novel effector on certain cells. Competitive binding assays demonstrated that mIL-20R1a bound to cell surfaces and resulted in AKT and JNK phosphorylation in primary mesangial cells (MCs) isolated from either the wild-type mice, DBA/W mice, or the SLE-prone mice, NZB/W mice. NZB/W MCs expressed more mIL-20R1a transcript than DBA/W MCs did. Furthermore, mIL-20R1a-treated NZB/W MCs produced higher level of chemokines, renal fibrogenic factors and ROS than mIL-20R1a-treated DBA/W MCs did. These factors are involved in the pathogenesis of lupus nephritis. Endogenous mIL-20R1a was upregulated in the bladder, colon and spleen tissue of NZB/W mice. Elevated mIL-20R1a in the spleen tissue of NZB/W mice was expressed mainly in monocytes and B cells. mIL-20R1a further induced mIL-10 production by the anti-IgM antibody-stimulated B cells in NZB/W mice. Therefore, mIL-20R1a-mediated effects may exacerbate the disease outcome of lupus nephritis.