Inflammatory cytokines in vitro production are associated with Ala16Val superoxide dismutase gene polymorphism of peripheral blood mononuclear cells.
Obesity is considered a chronic low-grade inflammatory state associated with a chronic oxidative stress caused by superoxide production (O(2)(-)). The superoxide dismutase manganese dependent (SOD2) catalyzes O(2)(-) in H(2)O(2) into mitochondria and is encoded by a single gene that presents a common polymorphism that results in the replacement of alanine (A) with a valine (V) in the 16 codon. This polymorphism has been implicated in a decreased efficiency of SOD2 transport into targeted mitochondria in V allele carriers. Previous studies described an association between VV genotype and metabolic diseases, including obesity and diabetes. However, the causal mechanisms to explain this association need to be more elucidated. We postulated that the polymorphism could influence the inflammatory response. To test our hypothesis, we evaluated the in vitro cytokines production by human peripheral blood mononuclear cells (PBMCs) carrier's different Ala16Val-SOD2 genotypes (IL-1, IL-6, IL-10, TNF-α, IFN-γ). Additionally, we evaluated if the culture medium glucose, enriched insulin, could influence the cytokine production. Higher levels of proinflammatory cytokines were observed in VV-PBMCs when compared to AA-PBMCs. However, the culture medium glucose and enriched insulin did not affect cytokine production. The results suggest that Ala16Val-SOD2 gene polymorphism could trigger the PBMCs proinflammatory cytokines level. However, discerning if a similar mechanism occurs in fat cells is an open question.
Laboratory of Molecular Aspects Associated to Genetic Diseases, University of Western Santa Catarina, Unoesc, Brazil.
Marco Aurélio Echart
MA
Montano
Ivana Beatrice Mânica
IB
da Cruz
Marta Maria Medeiros Frescura
MM
Duarte
Cristina da Costa
Cda C
Krewer
Maria Izabel de Ugalde Marques
MI
da Rocha
Maria Fernanda
MF
Mânica-Cattani
Felix Alexandre Antunes
FA
Soares
Guilherme
G
Rosa
Angélica Francesca
AF
Maris
Francielle Garghetti
FG
Battiston
Alexis
A
Trott
Juan Pablo Barrio
JP
Lera
D000409:Alanine / Q000235:genetics; D019943:Amino Acid Substitution; D002478:Cells, Cultured; D003470:Culture Media / Q000494:pharmacology; D016207:Cytokines / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005838:Genotype; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000097:blood; D018836:Inflammation Mediators / Q000097:blood; D007328:Insulin / Q000494:pharmacology; D007371:Interferon-gamma / Q000097:blood; D007375:Interleukin-1 / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011110:Polymorphism, Genetic; D013482:Superoxide Dismutase / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014633:Valine / Q000235:genetics; D000099156:Superoxide Dismutase 2
D000409:Alanine; D003470:Culture Media; D016207:Cytokines; D005947:Glucose; D018836:Inflammation Mediators; D007328:Insulin; D007371:Interferon-gamma; D007375:Interleukin-1; D016753:Interleukin-10; D015850:Interleukin-6; D013482:Superoxide Dismutase; D014409:Tumor Necrosis Factor-alpha; D014633:Valine; D000099156:Superoxide Dismutase 2