Recombinant Bet v 1-BanLec chimera modulates functional characteristics of peritoneal murine macrophages by promoting IL-10 secretion
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2021
Authors
Protić-Rosić, IsidoraNešić, Andrijana
Lukić, Ivana
Miljković, Radmila
Popović, Dragan
Atanasković-Marković, Marina
Stojanović, Marijana
Gavrović-Jankulović, Marija
Article (Published version)
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Show full item recordAbstract
Allergen-specific immunotherapy (AIT) is a desensitizing treatment for allergic diseases that corrects the underlined pathological immune response to innocuous protein antigens, called allergens. Recombinant allergens employed in the AIT allowed the production of well-defined formulations that possessed consistent quality but were often less efficient than natural allergen extracts. Combining recombinant allergens with an adjuvant or immunomodulatory agent could improve AIT efficacy. This study aimed to perform structural and functional characterization of newly designed recombinant chimera composed of the Bet v 1, the major birch pollen allergen, and Banana Lectin (BanLec), TLR2, and CD14 binding protein, for the application in AIT. rBet v 1-BanLec chimera was designed in silico and expressed as a soluble fraction in Escherichia coli. Purified rBet v 1-BanLec (33.4 kDa) retained BanLec-associated biological activity of carbohydrate-binding and preserved IgE reactive epitopes of Bet v ...1. The chimera revealed secondary structures with predominant β sheets. The immunomodulatory capacity of rBet v 1-BanLec tested on macrophages showed changes in myeloperoxidase activity, reduced NO production, and significant alterations in the production of cytokines when compared to both rBanLec and rBet v 1. Comparing to rBet v 1, rBet v 1-BanLec was demonstrated to be more efficient promoter of IL-10 production as well as weaker inducer of NO production and secretion of pro-inflammatory cytokines TNFα, and IL-6. The ability of rBet v 1-BanLec to promote IL-10 in together with the preserved 3D structure of Bet v 1 part implies that the construct might exert a beneficial effect in the allergen-specific immunotherapy.
Keywords:
Allergy / Banana lectin / Bet v 1 / Immunotherapy / MacrophagesSource:
Molecular Immunology, 2021, 138, 58-67Publisher:
- Elsevier
Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200026 (University of Belgrade, Institute of Chemistry, Technology and Metallurgy - IChTM) (RS-MESTD-inst-2020-200026)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200177 (Immunology Research Centre 'Branislav Janković' Torlak, Belgrade) (RS-MESTD-inst-2020-200177)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200168 (University of Belgrade, Faculty of Chemistry) (RS-MESTD-inst-2020-200168)
DOI: 10.1016/j.molimm.2021.06.015
ISSN: 0161-5890
WoS: 000692562500007
Scopus: 2-s2.0-85111743256
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TorlakTY - JOUR AU - Protić-Rosić, Isidora AU - Nešić, Andrijana AU - Lukić, Ivana AU - Miljković, Radmila AU - Popović, Dragan AU - Atanasković-Marković, Marina AU - Stojanović, Marijana AU - Gavrović-Jankulović, Marija PY - 2021 UR - http://intor.torlakinstitut.com/handle/123456789/630 AB - Allergen-specific immunotherapy (AIT) is a desensitizing treatment for allergic diseases that corrects the underlined pathological immune response to innocuous protein antigens, called allergens. Recombinant allergens employed in the AIT allowed the production of well-defined formulations that possessed consistent quality but were often less efficient than natural allergen extracts. Combining recombinant allergens with an adjuvant or immunomodulatory agent could improve AIT efficacy. This study aimed to perform structural and functional characterization of newly designed recombinant chimera composed of the Bet v 1, the major birch pollen allergen, and Banana Lectin (BanLec), TLR2, and CD14 binding protein, for the application in AIT. rBet v 1-BanLec chimera was designed in silico and expressed as a soluble fraction in Escherichia coli. Purified rBet v 1-BanLec (33.4 kDa) retained BanLec-associated biological activity of carbohydrate-binding and preserved IgE reactive epitopes of Bet v 1. The chimera revealed secondary structures with predominant β sheets. The immunomodulatory capacity of rBet v 1-BanLec tested on macrophages showed changes in myeloperoxidase activity, reduced NO production, and significant alterations in the production of cytokines when compared to both rBanLec and rBet v 1. Comparing to rBet v 1, rBet v 1-BanLec was demonstrated to be more efficient promoter of IL-10 production as well as weaker inducer of NO production and secretion of pro-inflammatory cytokines TNFα, and IL-6. The ability of rBet v 1-BanLec to promote IL-10 in together with the preserved 3D structure of Bet v 1 part implies that the construct might exert a beneficial effect in the allergen-specific immunotherapy. PB - Elsevier T2 - Molecular Immunology T1 - Recombinant Bet v 1-BanLec chimera modulates functional characteristics of peritoneal murine macrophages by promoting IL-10 secretion EP - 67 SP - 58 VL - 138 DO - 10.1016/j.molimm.2021.06.015 ER -
@article{ author = "Protić-Rosić, Isidora and Nešić, Andrijana and Lukić, Ivana and Miljković, Radmila and Popović, Dragan and Atanasković-Marković, Marina and Stojanović, Marijana and Gavrović-Jankulović, Marija", year = "2021", abstract = "Allergen-specific immunotherapy (AIT) is a desensitizing treatment for allergic diseases that corrects the underlined pathological immune response to innocuous protein antigens, called allergens. Recombinant allergens employed in the AIT allowed the production of well-defined formulations that possessed consistent quality but were often less efficient than natural allergen extracts. Combining recombinant allergens with an adjuvant or immunomodulatory agent could improve AIT efficacy. This study aimed to perform structural and functional characterization of newly designed recombinant chimera composed of the Bet v 1, the major birch pollen allergen, and Banana Lectin (BanLec), TLR2, and CD14 binding protein, for the application in AIT. rBet v 1-BanLec chimera was designed in silico and expressed as a soluble fraction in Escherichia coli. Purified rBet v 1-BanLec (33.4 kDa) retained BanLec-associated biological activity of carbohydrate-binding and preserved IgE reactive epitopes of Bet v 1. The chimera revealed secondary structures with predominant β sheets. The immunomodulatory capacity of rBet v 1-BanLec tested on macrophages showed changes in myeloperoxidase activity, reduced NO production, and significant alterations in the production of cytokines when compared to both rBanLec and rBet v 1. Comparing to rBet v 1, rBet v 1-BanLec was demonstrated to be more efficient promoter of IL-10 production as well as weaker inducer of NO production and secretion of pro-inflammatory cytokines TNFα, and IL-6. The ability of rBet v 1-BanLec to promote IL-10 in together with the preserved 3D structure of Bet v 1 part implies that the construct might exert a beneficial effect in the allergen-specific immunotherapy.", publisher = "Elsevier", journal = "Molecular Immunology", title = "Recombinant Bet v 1-BanLec chimera modulates functional characteristics of peritoneal murine macrophages by promoting IL-10 secretion", pages = "67-58", volume = "138", doi = "10.1016/j.molimm.2021.06.015" }
Protić-Rosić, I., Nešić, A., Lukić, I., Miljković, R., Popović, D., Atanasković-Marković, M., Stojanović, M.,& Gavrović-Jankulović, M.. (2021). Recombinant Bet v 1-BanLec chimera modulates functional characteristics of peritoneal murine macrophages by promoting IL-10 secretion. in Molecular Immunology Elsevier., 138, 58-67. https://doi.org/10.1016/j.molimm.2021.06.015
Protić-Rosić I, Nešić A, Lukić I, Miljković R, Popović D, Atanasković-Marković M, Stojanović M, Gavrović-Jankulović M. Recombinant Bet v 1-BanLec chimera modulates functional characteristics of peritoneal murine macrophages by promoting IL-10 secretion. in Molecular Immunology. 2021;138:58-67. doi:10.1016/j.molimm.2021.06.015 .
Protić-Rosić, Isidora, Nešić, Andrijana, Lukić, Ivana, Miljković, Radmila, Popović, Dragan, Atanasković-Marković, Marina, Stojanović, Marijana, Gavrović-Jankulović, Marija, "Recombinant Bet v 1-BanLec chimera modulates functional characteristics of peritoneal murine macrophages by promoting IL-10 secretion" in Molecular Immunology, 138 (2021):58-67, https://doi.org/10.1016/j.molimm.2021.06.015 . .