n-3 Fatty acids as resolvents of inflammation in the A549 cells.
BACKGROUND
Fatty acids and their derivatives are one of the most crucial inflammation mediators. The aim of our study was to evaluate the impact of polyunsaturated fatty acids as eicosanoids precursors on the A549 cell line.


METHODS
Cells were incubated with 40 μM of arachidonic, eicosapentaenoic or docosahexaenoic acid for 24h, then activated with LPS. Fatty acids content in the cell membranes were determined using gas chromatography. COX-2, cPGES and FP-receptor quantities were determined by Western blot. 8-Isoprostane F2α concentrations were determined by EIA. Maresin and protectin D1 contents were analyzed by UHPLC/MS-TOF method.


RESULTS
Significant differences in membrane fatty acids and levels of 8-isoPGF2α in the activated cells were detected. Elevated expression of COX-2 and FP-receptor was observed in cells treated with AA and activated with LPS. Moreover, compared to AA and AA+LPS groups, cells incubated with EPA, DHA, EPA+LPS and DHA+LPS showed decreased expression of COX-2, cPGES and FP-receptor. In cells incubated with EPA or DHA and activated with LPS maresin and protectin D1 were detected.


CONCLUSIONS
The results of the study have revealed the pro-inflammatory properties of AA, while the EPA and DHA had the opposite, resolving effect. Interestingly, FP-receptor inhibition by EPA and DHA demonstrated the unique role of the FP-receptor as a potential target for antagonists, in the diseases of inflammatory character. This study provides new information about n-3 fatty acids and their pro-resolving mediators, which can be used in the process of developing new anti-inflammatory drugs.
Department of Radioligands, Jagiellonian University Medical College, Faculty of Pharmacy, Kraków, Poland. Electronic address: jargasinska@cm-uj.krakow.pl.
Joanna
J
Gdula-Argasińska
Department of Infectious Diseases, Jagiellonian University Medical College, Faculty of Medicine, Kraków, Poland.
Jacek
J
Czepiel
Laboratory of Forensic Chemistry, Jagiellonian University, Faculty of Chemistry, Kraków, Poland.
Aneta
A
Woźniakiewicz
Department of Radioligands, Jagiellonian University Medical College, Faculty of Pharmacy, Kraków, Poland.
Katarzyna
K
Wojtoń
Department of Inorganic Chemistry, Jagiellonian University Medical College, Faculty of Pharmacy, Kraków, Poland.
Agata
A
Grzywacz
Laboratory of Forensic Chemistry, Jagiellonian University, Faculty of Chemistry, Kraków, Poland.
Michał
M
Woźniakiewicz
Department of Hematology, University Hospital, Kraków, Poland.
Artur
A
Jurczyszyn
Department of Medicine, University of Connecticut Health Center, Farmington, CT, USA.
William
W
Perucki
Department of Radioligands, Jagiellonian University Medical College, Faculty of Pharmacy, Kraków, Poland.
Tadeusz
T
Librowski
D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D015525:Fatty Acids, Omega-3; D018836:Inflammation Mediators
COX-2; FP-receptor; Fatty acids; Maresin; Protectin D1