TY - JOUR
T1 - Maintenance of NF-κB activation in T-lymphocytes and a naive T-cell population in autoimmune-prone (NZB/NZW)F1 mice by feeding a food-restricted diet enriched with n-3 fatty acids
AU - Jolly, Christopher A.
AU - Muthukumar, Alagarraju
AU - Reddy Avula, C. P.
AU - Fernandes, Gabriel
N1 - Funding Information:
This work was supported in part by NIH Grants F32 AG05826 (to C.A.J.) and RO1 AG13693 and RO1 AG14541 (to G.F.).
PY - 2001/11/1
Y1 - 2001/11/1
N2 - We have previously shown that feeding a fish oil (FO) supplemented diet in combination with 40% food restriction (FO/FR) has a greater impact on extending life span in lupus-prone (NZB × NZW)F1 mice than either FO ad libitum (FO/AL) or corn oil food restricted (CO/FR) alone. Lupus disease is associated with increased Th-2 (i.e., IL-6 and IL-10) cytokine production and reduced IL-2 production and NF-κB activation. We hypothesized that the mechanism of action by which FO/FR increases life span may involve alterations in T-lymphocyte signaling and subsequent cytokine production. To test this hypothesis, we isolated and then stimulated splenic T-lymphocytes ex vivo with anti-CD3 and -CD28 monoclonal antibodies. We report here that CO/FR and FO/FR and to a lesser extent FO/AL offset disease-associated losses in Th-1 cytokine production, CD69 expression, and NF-κB activation in splenic T-lymphocytes activated ex vivo. Similarly, CO/FR and FO/FR prevented the disease-dependent rise in Th-2 cytokine production ex vivo and CD69 expression in vivo. In essence, the T-lymphocyte phenotype in the old CO/FR and FO/FR groups was identical to that in the young disease-free mice. Taken together, the data suggest that both CO/FR and FO/FR increase life span, in part, by maintaining a youthful immune phenotype in autoimmune-prone mice. However, FO/FR appears to represent a more potent dietary strategy in delaying disease-associated immune dysregulation than CO/FR.
AB - We have previously shown that feeding a fish oil (FO) supplemented diet in combination with 40% food restriction (FO/FR) has a greater impact on extending life span in lupus-prone (NZB × NZW)F1 mice than either FO ad libitum (FO/AL) or corn oil food restricted (CO/FR) alone. Lupus disease is associated with increased Th-2 (i.e., IL-6 and IL-10) cytokine production and reduced IL-2 production and NF-κB activation. We hypothesized that the mechanism of action by which FO/FR increases life span may involve alterations in T-lymphocyte signaling and subsequent cytokine production. To test this hypothesis, we isolated and then stimulated splenic T-lymphocytes ex vivo with anti-CD3 and -CD28 monoclonal antibodies. We report here that CO/FR and FO/FR and to a lesser extent FO/AL offset disease-associated losses in Th-1 cytokine production, CD69 expression, and NF-κB activation in splenic T-lymphocytes activated ex vivo. Similarly, CO/FR and FO/FR prevented the disease-dependent rise in Th-2 cytokine production ex vivo and CD69 expression in vivo. In essence, the T-lymphocyte phenotype in the old CO/FR and FO/FR groups was identical to that in the young disease-free mice. Taken together, the data suggest that both CO/FR and FO/FR increase life span, in part, by maintaining a youthful immune phenotype in autoimmune-prone mice. However, FO/FR appears to represent a more potent dietary strategy in delaying disease-associated immune dysregulation than CO/FR.
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U2 - 10.1006/cimm.2001.1866
DO - 10.1006/cimm.2001.1866
M3 - Article
C2 - 11831874
AN - SCOPUS:0035498438
SN - 0008-8749
VL - 213
SP - 122
EP - 133
JO - Cellular Immunology
JF - Cellular Immunology
IS - 2
ER -