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A novel transcript of mouse interleukin-20 receptor acts on glomerular mesangial cells as an aggravating factor in lupus nephritis

Genes & Immunity volume 9, pages 668–679 (2008)Cite this article

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.

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Acknowledgements

This study was supported by a grant from the National Science Council (NSC 96-2628-B-006 -055 -MY3), Taiwan, Republic of China.

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Authors and Affiliations

  1. Institute of Basic Medical Sciences, Medical College, National Cheng Kung University, Tainan, Taiwan

    C-C Wei & M-S Chang

  2. Department of Medical Technology, Chung Hwa University of Medical Technology, Tainan, Taiwan

    C-C Wei

  3. Institute of Biopharmaceutical Sciences, Medical College, National Cheng Kung University, Tainan, Taiwan

    M-S Chang

  4. Graduate Institute of Biochemistry and Molecular Biology, Medical College, National Cheng Kung University, Tainan, Taiwan

    M-S Chang

  5. Department of Medical Research, Chi-Mei Medical Center, Tainan, Taiwan

    M-S Chang

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  1. C-C Wei
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Correspondence to M-S Chang.

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Wei, CC., Chang, MS. A novel transcript of mouse interleukin-20 receptor acts on glomerular mesangial cells as an aggravating factor in lupus nephritis. Genes Immun 9, 668–679 (2008). https://doi.org/10.1038/gene.2008.61

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