scholarly journals Delayed Cytokine mRNA Expression Kinetics after T-Lymphocyte Costimulation: A Quantitative Measure of the Efficacy of Cyclosporin A-based Immunosuppression

2002 ◽  
Vol 48 (12) ◽  
pp. 2225-2231 ◽  
Author(s):  
Christoph Härtel ◽  
Lutz Fricke ◽  
Nina Schumacher ◽  
Holger Kirchner ◽  
Michael Müller-Steinhardt
Keyword(s):  
T Cell ◽  
Mrna Expression ◽  
Kidney Transplant ◽  
Ex Vivo ◽  
Cytokine Mrna ◽  
Cytokine Mrna Expression ◽  
Tnf Α ◽  
Ex Vivo Study ◽  
Expression Kinetics

Abstract Background: Because cyclosporin A (CsA) and glucocorticoids inhibit the production of interleukin-2 (IL-2) and other cytokines, quantitative analysis of cytokine mRNA might constitute a pharmacodynamic measure for immunosuppressive drug effects. We investigated whether immunosuppressive drugs influence cytokine mRNA expression kinetics during T-cell costimulation. Methods: We used a human whole blood assay to determine basal (unstimulated) IL-2, IL-4, and tumor necrosis factor-α (TNF-α) mRNA concentrations and expression kinetics after anti-CD3/anti-CD28 monoclonal antibody costimulation in kidney transplant recipients undergoing CsA-based immunosuppressive triple therapy and in healthy controls (ex vivo study I). The effect of CsA on IL-2 mRNA expression kinetics was also determined ex vivo in patients undergoing CsA monotherapy (ex vivo study II) and after in vitro addition of CsA. Results: In ex vivo study I, basal TNF-α mRNA but not IL-2 and IL-4 mRNA was decreased in kidney transplant patients. We observed shifts in peak IL-2 and IL-4 (from 8 to 24 h) and TNF-α (from 4 to 8 h of costimulation) mRNA expression in kidney transplant patients after T-cell costimulation. In patients undergoing CsA monotherapy (ex vivo study II), the inhibitory effect of CsA was detectable as an individually delayed increase in IL-2 mRNA during costimulation. In vitro addition of CsA also induced a dose-independent displacement of IL-2 mRNA expression kinetics (i.e., a delay). Conclusions: A delayed increase in cytokine mRNA expression during T-cell costimulation may represent a sensitive effect of immunosuppression. The single analysis of one absolute or peak mRNA value could be misleading. For prospective studies involving measurement of cytokine mRNA, we therefore suggest the parameter “area of cytokine mRNA expression over time”, which should include absolute cytokine mRNA values at two different time points of mRNA kinetics.

Th2 Cytokine mRNA Expression in Skin in Cutaneous T-Cell Lymphoma

1994 ◽  
Vol 103 (5) ◽  
pp. 669-673 ◽  
Author(s):  
Benjamin R Vowels ◽  
Stuart R Lessin ◽  
Maureen Cassin ◽  
Christine Jaworsky ◽  
Bernice Benoit ◽  
...  
Keyword(s):  
T Cell ◽  
Mrna Expression ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Cutaneous T Cell Lymphoma ◽  
Cytokine Mrna ◽  
Cytokine Mrna Expression ◽  
Th2 Cytokine

The Role of IL-10 in iNOS and Cytokine mRNA Expression During In Vitro Differentiation of Bovine Mononuclear Phagocytes

1998 ◽  
Vol 18 (3) ◽  
pp. 139-149 ◽  
Author(s):  
WILL L. GOFF ◽  
KATHERINE I. O'ROURKE ◽  
W. CARL JOHNSON ◽  
PAUL A. LACY ◽  
WILLIAM C. DAVIS ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Mononuclear Phagocytes ◽  
In Vitro Differentiation ◽  
Cytokine Mrna ◽  
Cytokine Mrna Expression

scholarly journals Cytokine mRNA expression responses to resistance, aerobic, and concurrent exercise in sedentary middle-aged men

2014 ◽  
Vol 39 (2) ◽  
pp. 130-137 ◽  
Author(s):  
Cheyne E. Donges ◽  
Rob Duffield ◽  
Greg C. Smith ◽  
Michael J. Short ◽  
Johann A. Edge
Keyword(s):  
Mrna Expression ◽  
Vastus Lateralis ◽  
Receptor Expression ◽  
Middle Aged ◽  
Cytokine Mrna ◽  
Molecular Responses ◽  
Glycogen Concentration ◽  
Cytokine Mrna Expression ◽  
Tnf Α ◽  
Concurrent Exercise

Concurrent resistance and aerobic exercise (CE) is recommended to ageing populations, though is postulated to induce diminished acute molecular responses. Given that contraction-induced cytokine mRNA expression reportedly mediates remunerative postexercise molecular responses, it is necessary to determine whether cytokine mRNA expression may be diminished after CE. Eight middle-aged men (age, 53.3 ±1.8 years; body mass index, 29.4 ± 1.4 kg·m−2) randomly completed (balanced for completion order) 8 × 8 leg extensions at 70% maximal strength (RE), 40 min of cycling at 55% of peak aerobic workload (AE), or (workload-matched) 50% RE and 50% AE (CE). Muscle (vastus lateralis) was obtained pre-exercise, and at 1 h and 4 h postexercise, and analyzed for changes of glycogen concentration, tumor necrosis factor (TNF)α, TNF receptor-1 and -2 (TNF-R1 and TNF-R2, respectively), interleukin (IL)-6, IL-6R, IL-1β, and IL-1 receptor-antagonist (IL-1ra). All exercise modes upregulated cytokine mRNA expression at 1 h postexercise comparably (TNFα, TNF-R1, TNF-R2, IL-1β, IL-6) (p < 0.05). Expression remained elevated at 4 h after RE and AE (p < 0.05), though returned to pre-exercise levels after CE (p > 0.05). Moreover, AE and RE upregulated IL-1β and IL-1ra expression, whereas CE upregulated IL-1β expression only (p < 0.05). Only AE reduced muscle glycogen concentration (p < 0.05), whilst upregulating receptor expression the greatest; though, IL-6R expression remained unchanged after all modes (p > 0.05). In conclusion, in middle-aged men, all modes induced commensurate cytokine mRNA expression at 1 h postexercise; however, only CE resulted in ameliorated expression at 4 h postexercise. Whether the RE or AE components of CE are independently or cumulatively sufficient to upregulate cytokine responses, or whether they collectively inhibit cytokine mRNA expression, remains to be determined.

scholarly journals Heterogeneity of single cell cytokine gene expression in clonal T cell populations.

1994 ◽  
Vol 180 (4) ◽  
pp. 1251-1262 ◽  
Author(s):  
R P Bucy ◽  
A Panoskaltsis-Mortari ◽  
G Q Huang ◽  
J Li ◽  
L Karr ◽  
...  
Keyword(s):  
T Cell ◽  
Mrna Expression ◽  
Single Cell ◽  
Expression Level ◽  
Cytokine Gene ◽  
Cytokine Mrna ◽  
Ifn Gamma ◽  
Cytokine Genes ◽  
Cytokine Mrna Expression ◽  
Alpha Beta

T helper type 0 (Th0), Th1, and Th2 CD4+ T cell clones derived from a T cell receptor alpha/beta (TCR-alpha/beta) transgenic mouse were activated by antigen presented on "artificial" antigen-presenting cells that expressed or lacked the costimulatory molecule B7-1, and were analyzed for single cell cytokine mRNA expression by in situ hybridization. There was significant heterogeneity in the frequency of T cells that expressed individual cytokine mRNAs within each clonal population, suggesting that transcriptional control of each of the cytokine genes was not coordinate within an individual cell. The majority of antigen-stimulated Th1 cells expressed mRNA for interferon gamma (IFN-gamma), but far fewer cells in the same population expressed interleukin 2 (IL-2). Similarly, the frequency of IL-4-expressing cells was greater than that of IL-5- or IL-10-expressing cells in the same Th2 population, but the difference in expression frequencies was more variable between clones. The expression frequencies of each of the cytokines was quite heterogeneous in the antigen-activated Th0 population. The principal effect of increased antigen on the activation of individual cytokine genes in each of the clonal populations was to increase recruitment of mRNA-positive cells, with little or no effect on the level of cytokine mRNA expression in individual positive cells. The effects of B7 costimulation were variable depending on the cytokine gene analyzed. B7 costimulation markedly increased the frequency and the level of IL-2 mRNA expression in individual positive cells in the Th1 and Th0 populations, with less effect on the recruitment and single cell expression level of IFN-gamma. IL-4 frequencies were modestly increased by B7 costimulation of the Th2 clones, but there was no detectable increase in single cell IL-4 expression level. The observed patterns of cytokine mRNA expression favor a model of T cell activation in which all-or-none, rather than graded, responses of cytokine genes are dominant.

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