Role PKA and p38 MAPK on ROS production in neutrophil age-related: Lack of IL-10 effect in older subjects.
BACKGROUND
There is a large increase in the number of elderly people in modern societies. This demographic phenomenon has been paralleled by an epidemic of chronic diseases and inflammatory processes usually associated with advanced age.


OBJECTIVE
We studied the role of protein kinase A (PKA), protein kinase B (Akt/PKB) and p38 mitogen-activated protein kinase (p38 MAPK) signaling pathways in ROS produced by neutrophils induced by pro-interferon-gamma (IFN-gamma) or anti-inflammatory interleukin 10 (IL-10) cytokines age-related.


METHODS
The ROS generation was studied in healthy subjects in age ranging from 20 to 80 years old divided in five age groups: (20-39), (40-49), (50-59), (60-69) and (70-80) years old. ROS production was quantified in a luminol-dependent chemiluminescence assay and the results were expressed as relative light units/min).


RESULTS
ROS production in human neutrophil was activated by IFN-gamma in all the groups studied. This activation was down-regulated by IL-10. The inhibitory effect of IL-10 on 20-49 years old group was reversed by the pre-treatment with H89 (PKA inhibitor) but not with PD169316 (p38 MAPK inhibitor). This differential effect of IL-10 associated with age was not observed with the neutrophil pre-treatment with Akt/PKB or NADPH-oxidase inhibitor (DPI). Lack of IL-10 effect on ROS production was observed in older subjects (50-80 years old). The effect of IL-10 showed a significant inhibition of ROS production similar to those got with PD169316 alone as compared to that of p38 MAPK.


CONCLUSIONS
The results suggest that inhibitory effect of the ROS production mediated by IL-10 depends on PKA for the younger and the lack effect on the elderly is p38 MAPK dependent.
Chaves
Míriam Martins
MM
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. chavesmm@icb.ufmg.br
Costa
Daniela Caldeira
DC
de Oliveira
Bárbara Fonseca
BF
Rocha
Marcella Israel
MI
Nogueira-Machado
José Augusto
JA
D000368:Aged; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D016753:Interleukin-10 / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D004791:Enzyme Inhibitors; D007093:Imidazoles; D007546:Isoquinolines; D047428:Protein Kinase Inhibitors; D017382:Reactive Oxygen Species; D013449:Sulfonamides; D016753:Interleukin-10; D017868:Cyclic AMP-Dependent Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C408604:2-(4-nitrophenyl)-4-(4-fluorophenyl)-5-(4-pyridinyl)-1H-imidazole; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide