Production of biologically active recombinant buffalo leukemia inhibitory factor (BuLIF) in Escherichia Coli

Shradha Jamwal1, Shama Ansari1, Dhruba Malakar1, Jai Kumar Kaushik1, Sudarshan Kumar1, Ashok Kumar Mohanty2
1Animal Biotechnology Centre, ICAR-National Dairy Research Institute, Karnal, India
2Indian Council of Agricultural Research–Indian Veterinary Research Institute, Mukteshwar, India

Tóm tắt

Leukemia inhibitory factor (LIF) is a multifunctional cytokine which plays multiple roles in different biological processes such as implantation, bone remodeling, and hematopoiesis. The buESCs are difficult to culture due to lack of proper understanding of the culture conditions. LIF is one of the important factors which maintain the pluripotency in embryonic stem cells and commercial LIF from murine and human origin is used in the establishment of buffalo embryonic stem cells (buESCs). The LIF from a foreign origin is not able to maintain pluripotency and proliferation in buESCs for a long term which is contributed by difference in the binding sites on LIF; therefore, culture medium supplemented with buffalo-specific LIF may enhance the efficiency of buESCs by improving the environment of culture conditions. The high cost of LIF is another major drawback which restricts buESCs research, thus limits the scope of buffalo stem cell use. Various methods have been developed to produce human and murine LIF in prokaryotic system. However, Buffalo leukemia inhibitory factor (BuLIF) has not been yet produced in prokaryotic system. Here, we describe a simple strategy for the expression and purification of biologically active BuLIF in Escherichia coli (E. coli). The BuLIF cDNA from buffalo (Bubalus bubalis) was cloned into pET22b(+) and expressed in E. coli Lemo-21(DE3). The expression of BuLIF was directed into periplasmic space of E. coli which resulted in the formation of soluble recombinant protein. One step immobilized metal affinity chromatography (IMAC chromatography) was performed for purification of BuLIF with ≥ 95% of homogeneity. The recombinant protein was confirmed by western blot and identified by mass spectroscopy. The biological activity of recombinant BuLIF was determined on murine myeloid leukemic cells (M1 cells) by MTT proliferation assay. The addition of BuLIF increased the reduction of MTT by stimulated M1 cells in a dose-dependent manner. The BuLIF induced the formation of macrophage like structures from M1 cells where they engulfed fluorescent latex beads. The recombinant BuLIF successfully maintained pluripotency in buffalo embryonic stem cells (buESCs) and were positive for stem cells markers such as Oct-4, Sox-2, Nanog, and alkaline phosphatase activity. The present study demonstrated a simple method for the production of bioactive BuLIF in E. coli through single step purification. BuLIF effectively maintained buffalo embryonic stem cells pluripotency. Thus, this purified BuLIF can be used in stem cell study, biomedical, and agricultural research.

Tài liệu tham khảo

Heinrich PC, Behrmann I, Haan S, Hermanns HM, Müller-Newen G, Schaper F (2003) Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J 374(1):1–20. https://doi.org/10.1042/bj20030407 Tai CI, Ying QL (2013) Gbx2, a LIF/Stat3 target, promotes reprogramming to and retention of the pluripotent ground state. J Cell Sci 126:1093–1098. https://doi.org/10.1242/jcs.118273 Metcalfe SM (2011) LIF in the regulation of T-cell fate and as a potential therapeutic. Genes Immun 12(3):157–168. https://doi.org/10.1038/gene.2011.9 Nicola NA, Babon JJ (2015) Leukemia inhibitory factor (LIF). Cytokine Growth Factor Rev 26(5):533–544. https://doi.org/10.1016/j.cytogfr.2015.07.001 Huang C, Sun H, Wang Z, Liu Y, Cheng X, Liu J, Jiang Y (2018) Increased Krüppel-like factor 12 impairs embryo attachment via downregulation of leukemia inhibitory factor in women with recurrent implantation failure. Cell Death Dis 4:86. https://doi.org/10.1038/s41420-018-0088-8 Jung AS, Koo BK, Chong SH, Kim K, Choi DK, Thi Vu TT, Nguyen MT, Jeong B, Ryu HB, Kim I, Jang YJ (2013) Soluble expression of human leukemia inhibitory factor with protein disulfide isomerase in Escherichia coli and its simple purification. PLoS One 8(12):1–12. https://doi.org/10.1371/journal.pone.0083781 Smith SK, Charnock-Jones DS, Sharkey AM (1998) The role of leukemia inhibitory factor and interleukin-6 in human reproduction. Hum Reprod 3:237–243. https://doi.org/10.1093/humrep/13.suppl_3.237 Kimber SJ (2005) Leukaemia inhibitory factor in implantation and uterine biology. Repro 130(2):131–145. https://doi.org/10.1530/rep.1.00304 Lass A, Weiser W, Munafo A, Loumaye E (2001) Leukemia inhibitory factor in human reproduction. Fertlty Sterlty 76(6):1091–1096. https://doi.org/10.1016/S0015-0282(01)02878-3 Winship A, Correia J, Krishnan T, Menkhorst E, Cuman C, Zhang JG, Dimitriadis E (2015) Blocking endogenous leukemia inhibitory factor during placental development in mice leads to abnormal placentation and pregnancy loss. Sci Report 5(1):1–15. https://doi.org/10.1038/srep13237 Cheung L, Leung H, Bongso A (2003) Effect of supplementation of leukemia inhibitory factor and epidermal growth factor on murine embryonic development in vitro, implantation , and outcome of offspring. Fertil Steril 2:727–735. https://doi.org/10.1016/s0015-0282(03)00772-6 Roh S, Kim SW, Jung YG, Park JI (2016) Improvement of pregnancy rate by intrauterine administration of dexamethasone and recombinant human leukemia inhibitory factor at the time of embryo transfer in cattle. J Vet Sci 17(4):569–576. https://doi.org/10.4142/jvs.2016.17.4.569 Brinsden PR, Alam V, de Moustier B, Engrand P (2009) Recombinant human leukemia inhibitory factor does not improve implantation and pregnancy outcomes after assisted reproductive techniques in women with recurrent unexplained implantation failure. Fert and sterlty 91(4):1445–1447. https://doi.org/10.1016/j.fertnstert.2008.06.047 Lebkowski JS, Gold J, Xu C, Funk W, Chiu CP, Carpenter MK (2007) Human embryonic stem cells: culture, differentiation, and genetic modification for regenerative medicine applications. Cancer J (Sudbury Mass) 7:83–93 Imaizumi K, Nishikawa SI, Tarui H, Akuta T (2013) High-level expression and efficient one-step chromatographic purification of a soluble human leukemia inhibitory factor (LIF) in Escherichia coli. Prot Exprssn Purfctn 90(1):20–26. https://doi.org/10.1016/j.pep.2013.04.006 Ali SA, Malakar D, Kaushik JK, Mohanty AK, Kumar S (2018) Recombinant purified buffalo leukemia inhibitory factor plays an inhibitory role in cell growth. PLoS One 13(6):e0198523. https://doi.org/10.1371/journal.pone.0198523 Layton MJ, Lock P, Metcalf D, Nicola NA (1994) Cross-species receptor binding characteristics of human and mouse leukemia inhibitory factor suggest a complex binding interaction. J Bio Chem 269(25):17048–17055 Layton MJ, Owczarek CM, Metcalf D, Clark RL, Smith DK, Treutlein HR, Nicola NA (1994) Conversion of the biological specificity of murine to human leukemia inhibitory factor by replacing 6 amino acid residues. J Bio Chem 269(47):29891–29896 Tomala M, Lavrentieva A, Moretti P, Rinas U, Kasper C, Stahl F, Scheper T (2010) Preparation of bioactive soluble human leukemia inhibitory factor from recombinant Escherichia coli using thioredoxin as fusion partner. Prot Exprssn Purfctn 73(1):51–57. https://doi.org/10.1016/j.pep.2010.04.002 Guo Y, Yu M, Jing N, Zhang S (2018) Production of soluble bioactive mouse leukemia inhibitory factor from Escherichia coli using MBP tag. Protein Expr Purif 150:86–91. https://doi.org/10.1016/j.pep.2018.05.006 Imsoonthornruksa S, Noisa P, Parnpai R, Ketudat-Cairns M (2011) A simple method for production and purification of soluble and biologically active recombinant human leukemia inhibitory factor (hLIF) fusion protein in Escherichia coli. J Biotechnol 151(4):295–302. https://doi.org/10.1016/j.jbiotec.2010.12.020 Sockolosky JT, Szoka FC (2013) Periplasmic production via the pET expression system of soluble, bioactive human growth hormone. Prot Exprssn Purfctn 87(2):129–135. https://doi.org/10.1016/j.pep.2012.11.002 Zare F, Saboor-Yaraghi AA, Hadinedoushan H, Dehghan-Manshadi M, Mirzaei F, Mansouri F, Amiri MM (2020) Production and characterization of recombinant human leukemia inhibitory factor and evaluation of anti-fertility effects of rabbit anti-rhLIF in Balb/c mice. Prot Exprssn Purfctn 174:105684. https://doi.org/10.1016/j.pep.2020.105684 Anand T, Kumar D, Singh MK, Shah RA, Chauhan MS, Manik RS, Singla SK, Palta P (2011) Buffalo (Bubalus bubalis) embryonic stem cell-like cells and preimplantation embryos exhibit comparable expression of pluripotency-related antigens. Reprod Domes Anim 46(1):50–58. https://doi.org/10.1111/j.1439-0531.2009.01564.x Rawat P, Bathla S, Baithalu R, Yadav ML, Kumar S, Ali SA, Tiwari A, Lotfan M, Naru J, Jena M, Behere P (2016) Identification of potential protein biomarkers for early detection of pregnancy in cow urine using 2D DIGE and label free quantitation. Clin Proteomics 13(1):1–4. https://doi.org/10.1186/s12014-016-9116-y Wang L, Duan E, Sung LY, Jeong BS, Yang X, Tian XC (2005) Generation and characterization of pluripotent stem cells from cloned bovine embryos. Biol Reprod 73(1):149–155. https://doi.org/10.1095/biolreprod.104.037150 Choi TJ, Geletu TT (2018) High level expression and purification of recombinant flounder growth hormone in E. coli. J Genet Eng Biotechnol 16(2):347–355. https://doi.org/10.1016/j.jgeb.2018.03.006 Xi X, Li X, Wu F, Guan X, Jin L, Guo Y, Song W, Du B (2017) Expression, purification and characterization of active untagged recombinant human leukemia inhibitory factor from E.coli. Prot Exprssn Purfctn 134:139–146. https://doi.org/10.1016/j.pep.2017.03.020 San-Miguel T, Pérez-Bermúdez P, Gavidia I (2013) Production of soluble eukaryotic recombinant proteins in E. coli is favoured in early log-phase cultures induced at low temperature. Springerplus 2(1):1–4. https://doi.org/10.1186/2193-1801-2-89 Chevallet M, Luche S, Rabilloud T (2006) Silver staining of proteins in polyacrylamide gels. Nat Protoc 1(4):1852–1858. https://doi.org/10.1038/nprot.2006.288 Ohno M, Abe T (1991) Rapid colorimetric assay for the quantification of leukemia inhibitory factor (LIF) and interleukin-6 (IL-6). J Immuno Methds 145(1–2):199–203. https://doi.org/10.1016/0022-1759(91)90327-C Costa S, Almeida A, Castro A, Domingues L (2014) Fusion tags for protein solubility, purification, and immunogenicity in Escherichia coli: the novel Fh8 system. Front Microbiol:1–20. https://doi.org/10.3389/fmicb.2014.00063 Luo D, Wen C, Zhao R, Liu X, Liu X, Cui J, Liang P (2016) High level expression and purification of recombinant proteins from Escherichia coli with AK-TAG. PLoS One 11(5):1–11. https://doi.org/10.1371/journal.pone.0156106 Zhang W, Lu J, Zhang S, Liu L, Pang X, Lv J (2018) Development an effective system to expression recombinant protein in E. coli via comparison and optimization of signal peptides: expression of pseudomonas fuorescens BJ-10 thermostable lipase as case study. Microb Cell Factories 17(1):1–12. https://doi.org/10.1186/s12934-018-0894-y French C, Keshavarz-Moore E, Ward JM (1996) Development of a simple method for the recovery of recombinant proteins from the Escherichia coli periplasm. Enzym Microb Technol 19(5):332–338. https://doi.org/10.1016/S0141-0229(96)00003-8 Ralph P, Ho MK, Litcofsky PB, Springer TA (1983) Expression and induction in vitro of macrophage differentiation antigens on murine cell lines. J Immunol 130(1):108–14. Cambier N, Zhang Y, Vairo G, Kosmopoulos K, Metcalf D, Nicola NA, Elefanty AG (1999) Expression of BCR-ABL in M1 myeloid leukemia cells induces differentiation without arresting proliferation. Oncogene 18:343–352. https://doi.org/10.1038/sj.onc.1202302 Wu X, Song M, Yang X, Liu X, Liu K, Jiao C, Wang J, Bai C, Su G, Liu X, Li G (2016) Establishment of bovine embryonic stem cells after knockdown of CDX2. Sci Report 6(1):1–12. https://doi.org/10.1038/srep28343 Xue F, Ma Y, Chen YE, Zhang J, Lin TA, Chen CH, Lin WW, Roach M, Ju JC, Yang L, Du F, Xu J (2012) Recombinant rabbit leukemia inhibitory factor and rabbit embryonic fibroblasts support the derivation and maintenance of rabbit embryonic stem cells. Cell Rep 14(4):364–376. https://doi.org/10.1089/cell.2012.0001