Naslov (srp)

Uloga galektina 3 u eksperimentalnom modelu akutnog pankreatitisa

Autor

Stojanović, Bojan, 1986-, 35112807

Doprinosi

Lukić, Miodrag L., 1941-, 13590887
Jovanović, Ivan, 1977-, 3999847
Vojvodić, Danilo, 1963-, 10764647
Cvetković, Aleksandar, 1977-, 25746791

Opis (srp)

Uvod: Akutni pankreatitis se karakteriše autodigestijom panckreasnih ćelija što je potom praćeno akutnom inflamacijom koja doprinosi razvoju patoloških promena i smrtnom ishodu. U eksperimentalnim uslovima je pokazano da galektin 3 eksprimiraju acinusne ćelije i infiltrišući makrofagi, ali je nepoznata uloga ovog lektina u razvoju akutnog pankreatitisa. Materijal i metode: Akutni pankreatitis je uzrokovan podvezivanjem biliopankreatinog duktusa ili sekvencijalnom i intraperitonealnom primenom ceruleina i lipopolisaharida kod miševa divljeg soja i miševa sa delecijom gena za galektin 3. Rezultati: Delecija galektina 3 je poboljšala preživljavanje miševa usled smanjenja težine inflamacije pankreasa što je praćeno redukovanim leukocitnim infiltratom, nižim vrednostima amilaza u serumu i aktivnošću tripsina u pankreasu, smanjenom infiltracijom makrofaga i neutrofila koji eksprimiraju TLR-4, a posebno proinflamacijskih neutrofila. Galektin 3 i TLR-4 su kolokalizovani na površini leukocita u infiltratu. Primena inhibitora TLR-4, CLI-095, poboljšala je preživljavanje obolelih miševa. Nedostatak galektina 3 je praćen manjom produkcijom TNF-α i IL-1β iz makrofaga i dendritskih ćelija. Delecija gena za galetin 3 je praćena i manjom produkcijom IFN-γ iz T limfocita, NK i NKT ćelija, manja je aktivacija IL- 23/IL-17 osovine i povećana je infiltracija regulatornih T limfocita koji produkuju IL-10 u pankreasu izolovanog iz obolelih miševa. Zaključak: Delecija galektina 3 smanjuje težinu akutnog pankreatitisa u dva eksperimentalna modela bolesti uticajem na influks neutrofila i mononuklearnih ćelija urođene i stečene imunosti. Ove injenice ukazuju da primena inhibitora galektina 3 može imati povoljan efekat na progresiju akutnog pankreatitisa.

Opis (eng)

Introduction: Acute pancreatitis is characterized by autodigestion of pancreatic cells followed by acute inflammation leading to pathology and death. In experimental acute pancreatitis, pancreatic acinar cells and infiltrating macrophages express Galectin-3 but its role in pathology is unknown. Material and methods: Acute pancreatitis was induced by ligation of bile-pancreatic duct or sequential peritoneal administration of cerulein and lipopolysaccharide to wild-type and Galectin-3 deficient C57BL/6 mice. We determined survival of mice, serum concentrations of amylase, pancreatic pathology, and phenotypic and molecular features of inflammatory cells. Therefore, we studied its role using Galectin-3 deficient mice. Results: Deletion of Galectin-3 prolonged survival of mice contributed to attenuation of histopathology, reduced leukocytes infiltration, lowered serum amylase concentration and pancreatic trypsin activity, and decreased infiltration of macrophages and neutrophils that express TLR-4, in particular, pro-inflammatory N1 neutrophils. Galectin-3 and TLR-4 are also colocalized on infiltrating cells. Additionally, administration of CLI-095, the specific inhibitor of TLR-4, prolonged survival of diseased animals. Furthermore, lack of Galectin-3 reduced expression of pro-inflammatory TNF-α and IL-1β in F4/80+CD11c- macrophages and CD11c+F4/80- dendritic cells. Gal-3 deficiency decreased the total number of IFN-γ- producing CD3+CD49- T cells, CD3-CD49+ NK cells, and CD3+CD49+ NKT cells; downregulated activation of IL-23/IL-17 axis and increased accumulation of IL-10-producing Foxp3+ T regulatory cells in pancreata of diseased animals. Conclusion: Deletion of Galectin-3 ameliorates acute pancreatitis in the two experimental models by attenuating early influx of neutrophils and inflammatory mononuclear cells of innate and acquired immunity. These findings provide the basis to consider Galectin-3 as a therapeutic target in acute pancreatitis.

Jezik

srpski

Datum

2019

Licenca

Ovo delo je licencirano pod uslovima licence
Creative Commons CC BY-NC-ND 2.0 AT - Creative Commons Autorstvo - Nekomercijalno - Bez prerada 2.0 Austria License.

CC BY-NC-ND 2.0 AT

http://creativecommons.org/licenses/by-nc-nd/2.0/at/