THE ROLE OF NF-κB IN THE DIFFERENTIATION AND ACTIVATION OF NEUTROPHILS DURING THE BURN WOUND HEALING OF THE SKIN IN RATS
L.V. Natrus1, I.M. Ryzhko1, O.O. Lisakovska2, A.O. Tykhomyrov2, D.O. Labudzinskyi2, T.I. Panova3
- Research Institute of Experimental and Clinical Medicine
Bogomolets National Medical University, Kyiv, Ukraine
- Palladin Institute of Biochemistry NAS of Ukraine, Kyiv, Ukraine
- Bogomolets National Medical University, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz65.06.094

Abstract
We investigated the link between levels of key regulatory
pro-inflammatory proteins (nuclear factor kappa B (NF-κB),
it’s inhibitory subunit κB-α (IκB-α), vascular endothelial
growth-factor A (VEGF-A) and endothelial receptor FLT1)
in a connective tissue regenerate and changes in bone marrow
granulocyte and peripheral blood neutrophils counts during
the skin burn wound healing (on the 3,7,14,21st day) in
Wistar rats. It was detected a correlation between the NF-
κB contents and the granulocytes count r=0.739 (P <0.01);
between the neutrophils count and the VEGF-A contents r =
0.708 (P<0.01); between the FLT1contents and the VEGF-A
contents r = 0.865 (P <0.01); between the neutrophils contents
and the FLT1 contents (r = 0.472, P <0.05). The obtained
data provided the basis for formation of a hypothetical
multi-level regulatory chain in the system of connective
tissue - bone marrow - peripheral blood, appearing under the
normal physiological condition and possible key mechanism
of angiogenesis regulation. NF-κB probably activates the
production of myeloid progenitor growth factors and regulates
the differentiation of granulocytes in the bone marrow;
neutrophils from the blood enter the damaged area of the
burn wound, secrete endothelial growth factors and stimulate
the expression of endothelial receptors to these ligands in the
connective tissue regenerate.
Keywords:
skin regeneration, wound, bone marrow, neutrophils, angiogenesis.
References
- Pittman K, Kubes P. Damage-associated molecular patterns control neutrophil recruitment. J Innate Immun. 2013; 5:315-23.
CrossRef
PubMed PubMedCentral
- Ambrozova N, Ulrichova J, Galandakova A. Models for the study of skin wound healing. The role of NRF2 and NF-ΚB. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2017;161(1):1-13.
CrossRef
PubMed
- Oeckinghaus A, Ghosh S. The NF-kappaB family of transcription factors and its regulation. Cold Spring Harb Perspect Biol. 2009;1(4).
CrossRef
PubMed PubMedCentral
- Duran A, Diaz-Meco MT, Moscat J. Essential role of RelA Ser311 phosphorylation by zetaPKC in NF-κB transcriptional activation. EMBO J. 2003;22:3910-18.
CrossRef
PubMed PubMedCentral
- Sun SC. The non-canonical NF-κB pathway in immunity and inflammation. Nat Rev Immunol. 2017;17(9):545-58.
CrossRef
PubMed PubMedCentral
- Lawrence T. The Nuclear Factor NF-κB Pathway in Inflammation. Cold Spring Harb Perspect Biol. 2009;1(6):a001651.
CrossRef
PubMed PubMedCentral
- Cañedo-Dorantes L, Cañedo-Ayala M. Skin Acute Wound Healing: A Comprehensive Review. Int J Inflam. 2019;1(15):3706315.
CrossRef
PubMed PubMedCentral
- Gardner JC, Noel JG, Nikolaidis NM, Karns R, Aronow BJ, Ogle CK, McCormack FX. G-CSF drives a posttraumatic immune program that protects the host from infection. J Immunol. 2014;192(5):2405-17.
CrossRef
PubMed PubMedCentral
- Su Y, Richmond A. Chemokine Regulation of Neutrophil Infiltration of Skin Wounds. Adv Wound Care (New Rochelle). 2015;1;4(11):631-40.
CrossRef
PubMed PubMedCentral
- Wang J. Neutrophils in tissue injury and repair. Cell Tissue Res. 2018;371(3):531-9.
CrossRef
PubMed PubMedCentral
- Gong Y, Koh DR. Neutrophils promote inflammatory angiogenesis via release of preformed VEGF in an in vivo corneal model. Cell Tissue Res. 2010;339:437-48.
CrossRef
PubMed
- Grunewald M, Avraham I, Dor Y, Bachar-Lustig E, Itin A, Jung S, Chimenti S, Landsman L, Abramovitch R, Keshet E. VEGF-induced adult neovascularization: recruitment, retention, and role of accessory cells. Cell. 2006;13;124(1):175-89.
CrossRef
PubMed
- Kolesova NA, Natrus LV, Litvinenko VI, Sukhareva NM, Ryzhko IM. Dynamic of connective-tissue cell reactions of the skin of white rats with burn injury and persistent uncorrected hyperglycemia. Med Sci Ukraine. 2016;12(3-4):4-11.
- Natrus L, Ryzhko I, Kozak A, Kryvosheieva O, Stechenko L. Ultrastructural base of the connective tissue skin' cells interactions at burn injury in the hyperglycemic white rats. Svit Medytsyny ta Biol. 2017;4(62):157-62.
CrossRef
- Gordon S, Taylor PR. Monocyte and macrophage heterogeneity. Nat Rev Immunol. 2005; 5(12):953-64.
CrossRef
PubMed
- Dalli J, Montero-Melendez T, Norling LV, Yin X, Hinds C, Haskard D, Mayr M, Perretti M. Heterogeneity in neutrophil microparticles reveals distinct proteome and functional properties. Mol Cell Proteomics. 2013;12:2205-19.
CrossRef
PubMed PubMedCentral
- Soehnlein O, Lindbom L. Phagocyte partnership during the onset and resolution of inflammation. Nat Rev Immunol. 2010;10:427-39.
CrossRef
PubMed
- Kolaczkowska E, Kubes P. Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol. 2013;13:159-75.
CrossRef
PubMed
- Massena S, Christoffersson G, Vågesjö E. Identification and characterization of VEGF-A-responsive neutrophils expressing CD49d, VEGFR1, and CXCR4 in mice and humans. Blood. 2015;22;126(17):2016-26.
CrossRef
PubMed PubMedCentral
- Peiseler M, Kubes P. More friend than foe: the emerging role of neutrophils in tissue repair. J Clin Invest. 2019;129(7):2629-39.
CrossRef
PubMed
|