Biomedical subjects

M A Pahlavani

Publications and source records attributed to M A Pahlavani.

10 recordsLinked to original sources

PubMed1996

The effect of age on the expression of interleukin-2.

Interleukin-2 (IL-2) is a growth promoting cytokine that has received a great deal of attention over the past decade with respect to aging and cancer. It is produced primarily by helper T cells and regulates the growth and function of various cells that are involved in cellular and humoral immunity. The expression of IL-2 has been found to decrease with age in humans and rodents. The decline in IL-2 production has been shown to parallel the age-related decrease in immunologic function. Several studies indicate that treatment of lymphocytes from old subjects with exogenous IL-2 or infusion of IL-2 into old animals partially or completely restores some of the immune functions that decline with age. The age-related decline in IL-2 production has been shown to arise from a decline in IL-2 transcription, and a recent study suggests that the transcription factor NFAT (nuclear factor of activated T cells) may play a role in the decline in IL-2 transcription.

Aging↗

PubMed1996

Expression of heat shock protein 70 in rat spleen lymphocytes is affected by age but not by food restriction.

The purpose of this study was to determine if food restriction alters the age-related decline in heat shock protein 70 (hsp70) expression in lymphocytes from male Fischer 344 rats. Spleen lymphocytes were isolated from young (6 mo) and old (24 mo) rats that had free access to food (control group) and from food-restricted old (24 mo) rats that, beginning at 6 wk of age, were fed 60% (40% food restriction) of the diet consumed by the control rats. Lymphocytes were either heat shocked (42.5 degrees C for 1 h) or maintained at 37 degrees C (control). The levels of hsp70 protein and mRNA and the induction of interleukin-2 (IL-2) mRNA by concanavalin A (conA) were measured in these rats. In addition, the percentage of viability (as an index of thermosensitivity) of the lymphocytes from these rats was also measured after exposure of cells to different temperatures (first at 42.5 degrees C and then 45 degrees C). We found that the induction of hsp70 protein and mRNA in lymphocytes isolated from control old rats and food-restricted old rats was lower (P < 0.001) than that in control young rats. However, the levels of hsp70 and mRNA in lymphocytes isolated from food-restricted old rats were similar to the levels in age-matched control rats. Lymphocytes from both control old rats and food-restricted old rats were more thermosensitive than lymphocytes from control young rats; however, thermosensitivity of lymphocytes from food-restricted old rats was similar to that of age-matched control rats. The induction of IL-2 mRNA levels by conA was significantly (P < 0.001) lower in old than in young control rats. In contrast to hsp70, which was not affected by food restriction, the induction of IL-2 mRNA was higher (P < 0.05) in food-restricted old rats than in age-matched control rats. Therefore, food restriction has a differential effect on gene expression.

Aging↗

PubMed1995

The age-related decline in the induction of IL-2 transcription is correlated to changes in the transcription factor NFAT.

The effect of aging on the induction of IL-2 transcription by concanavalin A was studied in spleen lymphocytes isolated from young (4-6 months) and old (24 months) male Fischer 344 rats. The induction of IL-2 mRNA levels and IL-2 transcription were 40 to 50% lower for spleen lymphocytes isolated from old rats compared to spleen lymphocytes isolated from young rats. Because the transcription factor NFAT (nuclear factor activating IL-2 transcription) plays a major role in the regulation of IL-2 transcription, the DNA binding activity of NFAT in nuclear extracts of concanavalin A-stimulated lymphocytes was measured using a gel shift assay. The ability of nuclear extracts isolated from either total spleen lymphocytes or T cells to bind the NFAT oligonucleotide decreased 50 to 60% with age. Therefore, the age-related decrease in the expression of IL-2 appears to occur at the level of transcription and involves the transcription factor NFAT.

Aging↗

PubMed1995

The expression of heat shock protein 70 decreases with age in lymphocytes from rats and rhesus monkeys.

The ability of cells to express heat shock proteins in response to a stress such as heat is universal to all organisms and is believed to play a critical protective role. Therefore, it was of interest to determine the influence of aging on the ability of lymphocytes to express the heat shock protein hsp70 in response to a heat shock (42.5 degrees C for 1 h). Splenic lymphocytes isolated from old (24-26 months) rats showed a marked decrease in the induction of hsp70 protein levels or hsp70 synthesis when compared to lymphocytes isolated from young (4-5 months) rats. An age-related decrease in the induction of hsp70 levels by heat also was observed in peripheral lymphocytes isolated from rhesus monkeys. The decline with age in the induction of hsp70 by lymphocytes from rats was paralleled by a decrease in the induction of hsp70 mRNA and the nuclear transcription of hsp70. In addition, it was found that the ability of extracts from heat-shocked lymphocytes to bind the heat shock element (HSE) decreased approximately 50% with age. Therefore, it appears that the reduced ability of lymphocytes from old rats to express hsp70 in response to a heat shock occurs at the level of transcription because of an alteration in the ability of the heat shock transcription factor to bind the HSE on the promoter of the hsp70 gene. The age-related decrease in the induction of hsp70 appears to be physiologically important because the viability of spleen lymphocytes exposed to high temperatures decreases significantly with age.

Aging↗

PubMed1994

Age-related decrease in the naive (OX22+) T cells in F344 rats.

The frequency of the cells bearing the naive marker (OX22+) in T cells, helper, and cytotoxic/suppressor T cell subsets isolated from the spleens of young and old F344 rats were measured by flow cytometry. The percentage of naive cells in T cells decreased significantly with age and this decline occurred primarily in the helper subset.

Aging↗

PubMed1991

T cell activation by mycobacterial antigens in inflammatory synovitis.

To define which mycobacterial antigens were responsible for the activation of synovial fluid T lymphocytes, acetone-precipitated Mycobacterium tuberculosis (AP-MT) antigens were separated into five fractions following polyacrylamide gel electrophoresis and added to the mononuclear cell cultures of patients with inflammatory synovitis. Fractions 2 (50 to 70 kDa) and 5 (less than 28 kDa) resulted in significantly more proliferation than that of fractions 1, 3, and 4. The response to a purified mycobacterial 65-kDa heat shock protein (hsp), which migrated in fraction 2, was highly correlated (r = 0.89, P less than 0.001) with the response to the crude AP-MT. The proliferative response to a different hsp. the Escherichia coli DnaK, by synovial fluid lymphocytes was marginal. Analysis of the synovial fluid T cell response to mycobacterial culture filtrates by T cell Western blotting revealed dominant responses to antigen(s) in the range of 31 to 21 kDa in each responding patient, although no other consistent pattern of T cell activation was noted. Three lines of evidence suggested that the response to the low molecular weight fractions was directed against degradation fragments of the 65-kDa protein. These observations suggest that the activation of T lymphocytes obtained from inflammatory synovial fluids by crude mycobacterial antigens was due in large part to recognition of the 65-kDa mycobacterial hsp.

Antigens, Bacterial↗

PubMed1989

Antigenic specificity of rheumatoid synovial fluid lymphocytes.

The majority of rheumatoid arthritis (RA) synovial fluid lymphocytes (SFL) demonstrate markers that are suggestive of prior activation. While the mechanism(s) responsible is unknown, prior studies have suggested that certain Mycobacterium tuberculosis (MT) antigens may preferentially activate SFL in vitro. We therefore examined the ability of RA SFL to respond to purified protein derivative and an acetone-precipitable MT antigenic complex (AP-MT) and compared this with the responses by peripheral blood lymphocytes (PBL). The responses were contrasted with those elicited with tetanus toxoid (TT) and mitogenic anti-CD3. In patients with RA, the SF proliferative responses to both TT and anti-CD3 were reduced compared with responses by PB. In contrast, the SF response to purified protein derivative was maintained, and that to AP-MT was significantly increased, compared with PB. SF responses to AP-MT antigens were significantly greater than those to TT. The AP-MT activation of T lymphocytes from RA SF was characterized by an earlier peak proliferative response than that noted with matched PB. AP-MT responsiveness was not restricted to HLA-DR4 positive patients. These observations suggest that an epitope(s) contained within the MT complex of antigens, and enriched in the AP-MT complex, may be important in maintaining the chronic inflammation in at least some patients with RA.

Acetone↗

PubMed1988

Influence of exercise on the immune function of rats of various ages.

The purpose of this study was to determine whether exercise could prevent the age-related decline in mitogenesis, which has been well documented in rats, mice, and humans. At 1, 6, 12, and 18 mo of age, male Fischer F344 rats were subjected daily to swimming exercise for 6 mo. At the end of the 6-mo training period, spleen lymphocytes were isolated from the exercised rats and from age-matched sedentary controls. The induction of lymphocyte proliferation was measured with the mitogens concanavalin A (ConA) and lipopolysaccharide (LPS). In addition, the ability of the lymphocytes to produce interleukin 2 (IL 2) in response to ConA induction was measured. ConA- and LPS-induced proliferation decreased 41-63% between 7 and 25 mo of age in both exercised and sedentary control rats. ConA-induced IL 2 production decreased 42 and 62% between 7 and 25 mo of age for exercised and sedentary control rats, respectively. Although the age-related decline in mitogen-induced proliferation and IL 2 production was smaller in exercised rats, this was due to a lower level of mitogenesis and IL 2 production in lymphocytes from young exercised rats. Exercise resulted in a significant decrease (23-32%) in mitogen-induced lymphocyte proliferation and IL-2 production in 7-mo-old exercised rats compared with 7-mo-old sedentary rats. However, in the 18- and 24-mo-old rats, mitogen-induced lymphocyte proliferation and IL 2 production was not significantly different between exercised and sedentary control rats.

Aging↗

PubMed1987

Age-dependent changes of the mesenteric lymph node of Fischer F344 rats: morphological and histometric analysis.

Changes in mesenteric lymph nodes from Fischer F344 rats ranging from 5 to 37 months were studied by histological and histometric techniques. The most drastic histological changes were observed between 12 and 37 months of age. These changes include: loss of cellularity in the cortex; decrease in the number of germinal centers; distension of the medullary sinuses; decrease in the ratio of cortical area to medullary area; and infiltration of fibroblastic cells in the cortex and the medulla. Our results indicate a general structural disorganization in the mesenteric lymph node with increasing age. Such structural disturbance might be an important extrinsic factor for the decline in lymphocyte functions.

Aging↗

PubMedDate not supplied

Effect of dehydroepiandrosterone on mitogen-induced lymphocyte proliferation and cytokine production in young and old F344 rats.

The steroid hormone intermediate, dehydroepiandrosterone (DHEA), has been proposed as a therapeutic agent for the treatment of immunosenescence in mouse model. In the present study, the in vitro effect of DHEA on mitogen-induced lymphocyte proliferation and cytokine production was evaluated in a rat model. Spleen lymphocytes were isolated from young (4-6 months) and old (24-26 months) F344 rats and were incubated with DHEA for 30 min. The induction of lymphocyte proliferation, interleukin-2 (IL-2), and interferon-gamma (IFN-gamma) production by concanavalin A (Con A) was measured in a culture medium supplemented with either fetal calf serum (FCS) or with serum-free medium (Nutridoma-SR, N-SR). The induction of lymphocyte proliferation and IL-2 production by Con A decreased significantly with age, whereas induction of IFN-gamma increased with age. Treatment of lymphocytes with DHEA did not significantly alter Con A-induced proliferation or the production of IL-2 or IFN-gamma by spleen lymphocytes isolated from either young or old rats. These data indicate that in vitro DHEA treatment appears to have no immunomodulatory effect on the age-related changes in mitogen-induced proliferation or cytokine production in rat lymphocytes.

Aging↗