Mudskipper interleukin-34 modulates the functions of monocytes/macrophages via the colony-stimulating factor-1 receptor 1  

作　　者：Hai-Yu Shen Yan Zhou Qian-Jin Zhou Ming-Yun Li Jiong Chen 

机构地区：[1]State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products,Ningbo University,Ningbo,Zhejiang 315211,China [2]Laboratory of Biochemistry and Molecular Biology,School of Marine Sciences,Ningbo University,Ningbo,Zhejiang 315832,China [3]Key Laboratory of Applied Marine Biotechnology of Ministry of Education,Ningbo University,Ningbo,Zhejiang 315832,China

出　　处：《Zoological Research》2020年第2期123-137,共15页动物学研究（英文）

基　　金：supported by the National Natural Science Foundation of China(31972821;31772876);the Program of Zhejiang Provincial Natural Science Foundation of China(LZ18C190001);Science and Technology Department of Zhejiang Province(LGN18C180002);Natural Science Foundation of Ningbo City(2018A610342);the K.C.Wong Magna Fund in Ningbo University。

摘　　要：Interleukin-34(IL-34)is a novel cytokine that plays an important role in innate immunity and inflammatory processes by binding to the colonystimulating factor-1 receptor(CSF-1R).However,information on the function of IL-34 in fish remains limited.In the present study,we identified an IL-34 homolog from mudskippers(Boleophthalmus pectinirostris).In silico analysis showed that the mudskipper IL-34(BpIL-34)was similar to other known IL-34 variants in sequence and structure and was most closely related to an orange-spotted grouper(Epinephelus coioides)homolog.BpIL-34 transcripts were constitutively expressed in various tissues,with the highest level of expression found in the brain.Edwardsiella tarda infection significantly up-regulated the mRNA expression of BpIL-34 in the mudskipper tissues.The recombinant mature BpIL-34 peptide(rBpIL-34)was purified and used to produce anti-rBpIL-34 IgG.Western blot analysis combined with PNGase F digestion revealed that native BpIL-34 in monocytes/macrophages(MOs/MФs)was N-glycosylated.In vitro,rBpIL-34 treatment enhanced the phagocytotic and bactericidal activity of mudskipper MOs/MФs,as well as the mRNA expression of pro-inflammatory cytokines like tumor necrosis factorα(BpTNF-α)and BpIL-1βin these cells.Furthermore,the knockdown of mudskipper CSF-1R1(BpCSF-1R1),but not mudskipper BpCSF-1R2,significantly inhibited the rBpIL-34-mediated enhanced effect on MO/MФfunction.In conclusion,our results indicate that mudskipper BpIL-34 modulates the functions of MOs/MФs via BpCSF-1R1.Interleukin-34(IL-34) is a novel cytokine that plays an important role in innate immunity and inflammatory processes by binding to the colonystimulating factor-1 receptor(CSF-1R). However,information on the function of IL-34 in fish remains limited. In the present study, we identified an IL-34 homologfrommudskippers(Boleophthalmus pectinirostris). In silico analysis showed that the mudskipper IL-34(BpIL-34) was similar to other known IL-34 variants in sequence and structure and was most closely related to an orange-spotted grouper(Epinephelus coioides) homolog. BpIL-34 transcripts were constitutively expressed in various tissues, with the highest level of expression found in the brain. Edwardsiella tarda infection significantly up-regulated the mRNA expression of BpIL-34 in the mudskipper tissues. The recombinant mature BpIL-34 peptide(rBpIL-34) was purified and used to produce anti-rBpIL-34 IgG. Western blot analysis combined with PNGase F digestion revealed that nativeBpIL-34 inmonocytes/macrophages(MOs/MФs) was N-glycosylated. In vitro, rBpIL-34 treatmentenhancedthephagocytoticand bactericidal activity of mudskipper MOs/MФs, as well as the mRNA expression of pro-inflammatory cytokines like tumor necrosis factor α(BpTNF-α) and BpIL-1β in these cells. Furthermore, the knockdown of mudskipper CSF-1R1(BpCSF-1R1), but not mudskipper BpCSF-1R2, significantly inhibited the rBpIL-34-mediated enhanced effect on MO/MФfunction. In conclusion, our results indicate that mudskipper BpIL-34 modulates the functions of MOs/MФs via BpCSF-1R1.

关 键 词：Interleukin-34 MUDSKIPPER MONOCYTE/MACROPHAGE function EDWARDSIELLA tarda Colonystimulating factor-1 RECEPTOR 

分 类 号：Q25[生物学—细胞生物学]