Abstract
Sj16, a 16-kDa protein secreted from Schistosoma japonicum, has been demonstrated an anti-inflammatory effect in vitro and in vivo, but its mechanism is still not clear. In this study, microarray analysis was performed to investigate the effects of recombinant Sj16 (rSj16) on the gene expression of the lipopolysaccharide (LPS)-stimulated dendritic cells (DCs). Immature DCs were treated with LPS, LPS + recombinant Sj16 (rSj16), or rSj16 alone for 24 h, and the gene expression profiles were examined using complementary DNA (cDNA) microarrays. With the cutoff value of 2-fold change in the expression, 509 genes were affected, 226 genes upregulated, and 283 genes downregulated after adding rSj16. Analysis by functional annotation clustering tool showed that rSj16-affected genes mainly associated with inflammatory response, defense response, regulation of immune system process, apoptosis, and cell migration. The results revealed that rSj16 reduced the LPS-induced pro-inflammatory genes such as cytokines (e.g., IL6, IL18, IFN-γ, IL12a, IL1b), chemokines, and receptors (e.g., CXCL1, CXCL9, CCL5, CCR5, CCR1, CCR2, CXCR3) and increased the anti-inflammatory gene IL-10. Further data mining of these genes by pathway analysis showed that genes regulated by rSj16 were significantly involved in cytokine-cytokine receptor interaction, NOD-like receptor signaling pathway, Toll-like receptor signaling pathway, antigen processing and presentation, and Jak-STAT signaling pathway. In addition, quantitative real-time PCR (qRT-PCR) and Western blot analysis showed that rSj16 downregulated the expression of inhibitor of nuclear factor kappa-β kinase subunit beta (IKKβ) and nuclear factor-kappa β p65 (NF-κβ) messenger RNA (mRNA) and inhibited the phosphorylation of IKKβ and the NF-κB p65 protein, which implied that rSj16 exerting immunomodulatory effects by suppressing NF-κB signaling pathway. These results provide useful information in further understanding of the immunoregulation mechanisms of Sj16, and it is indicated that Sj16 could be as a potential molecule for the immunosuppressant drug development.
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Acknowledgments
This work was supported by grants from the National Natural Science Foundation of China (no. 30972574 and 81201309) and a grant from the China Postdoctoral Science Foundation (no. 2011 M501363), the Natural Science Foundation of Guangdong Province, China (no. 3S2012040007256), and the Foundation of Doctoral Program of Higher Education of China (no. 20120171120049).
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Table S1
Changes in gene expression of the 35 genes common among three group treatments (LPS, rSj16 + LPS, and rSj16) (DOCX 24 kb)
Table S2
Gene expression profiles that were upregulated when cells that were treated with rSj16 + LPS were compared with those that were treated with LPS alone for 24 h (XLSX 45 kb)
Table S3
Gene expression profiles that were reversed when cells that were treated with rSj16 + LPS were compared with those that were treated with LPS alone for 24 h (XLSX 43 kb)
Table S4
Functional categorization of downregulated genes induced by rSj16 + LPS versus LPS treatment (P < 0.05) (XLSX 21 kb)
Table S5
Functional categorization of upregulated genes induced by rSj16 + LPS versus LPS treatment (P < 0.05) (XLSX 16 kb)
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Shen, J., Xu, L., Liu, Z. et al. Gene expression profile of LPS-stimulated dendritic cells induced by a recombinant Sj16 (rSj16) derived from Schistosoma japonicum . Parasitol Res 113, 3073–3083 (2014). https://doi.org/10.1007/s00436-014-3973-y
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DOI: https://doi.org/10.1007/s00436-014-3973-y