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

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.

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

Clinical Chemistry ◽

10.1093/clinchem/48.12.2225 ◽

2002 ◽

Vol 48 (12) ◽

pp. 2225-2231 ◽

Cited By ~ 43

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.

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Changes in urinary bladder cytokine mRNA and protein after cyclophosphamide-induced cystitis

Physiological Genomics ◽

10.1152/physiolgenomics.00117.2001 ◽

2002 ◽

Vol 9 (1) ◽

pp. 5-13 ◽

Cited By ~ 63

Author(s):

Susan E. Malley ◽

Margaret A. Vizzard

Keyword(s):

Urinary Bladder ◽

Protein Expression ◽

Mrna Expression ◽

Fold Increase ◽

Cytokine Expression ◽

Cytokine Mrna ◽

Rnase Protection ◽

Acute Cystitis ◽

Cytokine Mrna Expression ◽

Tnf Α

Cyclophosphamide (CYP)-induced cystitis alters micturition function and produces reorganization of the micturition reflex. This reorganization may involve cytokine expression in the urinary bladder. These studies have determined candidate cytokines in the bladder that may contribute to the reorganization process. An RNase protection assay was used to measure changes in rat bladder cytokine mRNA [interferon-γ (IFN)-γ, interleukin-1α/β (IL-1α/β), IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, and tumor necrosis factor-α/β (TNF-α/β)] after acute (4 h), intermediate (48 h), or chronic (10 day) cystitis. The correlation between bladder cytokine mRNA and protein expression was also determined by immunoassay. Although at each time point after cystitis significant changes in bladder cytokine mRNA were observed, the magnitude differed (acute > intermediate > chronic). Acute cystitis demonstrated the most robust changes ( P ≤ 0.005; IL-1β, 330-fold increase; IL-2, 20-fold increase; IL-4, 8-fold increase; IL-6, 80-fold increase) in cytokine mRNA expression and TNF-α or TNF-β mRNA were only increased (2–10-fold) after acute cystitis. More modest increases in cytokine mRNA expression were observed after 48-h or 10-day cystitis. Cytokine protein expression generally paralleled that of mRNA. Increased cytokine expression after CYP-induced cystitis, alone or in combination with other inflammatory mediators or growth factors, may contribute to altered lower urinary tract function after cystitis.

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Cytokine mRNA Expression in Mycobacteriam ulcerans-Infected Human Skin and Correlation with Local Inflammatory Response

Infection and Immunity ◽

10.1128/iai.74.5.2917-2924.2006 ◽

2006 ◽

Vol 74 (5) ◽

pp. 2917-2924 ◽

Cited By ~ 25

Author(s):

R. Phillips ◽

C. Horsfield ◽

J. Mangan ◽

K. Laing ◽

S. Etuaful ◽

...

Keyword(s):

Mrna Expression ◽

Interleukin 10 ◽

Mycobacterium Ulcerans ◽

Cytokine Mrna ◽

Necrosis Factor Alpha ◽

Tissue Samples ◽

Local Inflammatory Response ◽

Cytokine Mrna Expression ◽

Tnf Α ◽

Ifn Γ

ABSTRACT Cytokine mRNA expression in biopsies of Mycobacterium ulcerans-infected human tissue was investigated using real-time PCR, and the findings were correlated with the clinical stages of disease and histopathologies. A broad range of cytokine mRNAs were detected in 16 early nodules and 28 late-stage ulcers, including those for the Th1 cytokines tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ) and the Th2 cytokine interleukin 10 (IL-10). IFN-γ was strongly expressed in both nodules and ulcers, suggesting that a Th1 response begins early in the disease. There was a significantly higher expression of IL-8 and other proinflammatory cytokines in results from 32 biopsies with neutrophilia than in those from 12 biopsies without acute inflammation. Ten tissue samples containing granulomas showed high mRNA expression for IFN-γ, IL-1β, IL-12p35, IL-12p40, IL-15, and TNF-α relative to 34 tissue samples without granulomas. These results suggest that the human immune response to M. ulcerans is similar to that seen with some other mycobacteria despite the presence of the toxin mycolactone in the tissues.

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Real-Time Reverse Transcription-PCR Quantification of Cytokine mRNA Expression in Golden Syrian Hamster Infected with Leishmania infantum and Treated with a New Amphotericin B Formulation

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.50.4.1195-1201.2006 ◽

2006 ◽

Vol 50 (4) ◽

pp. 1195-1201 ◽

Cited By ~ 21

Author(s):

S. Rama Iñiguez ◽

M. A. Dea-Ayuela ◽

J. A. Sanchez-Brunete ◽

J. J. Torrado ◽

J. M. Alunda ◽

...

Keyword(s):

Mrna Expression ◽

Reverse Transcription ◽

Syrian Hamster ◽

Leishmania Infantum ◽

Cytokine Mrna ◽

Golden Syrian Hamster ◽

Cytokine Mrna Expression ◽

Reverse Transcription Pcr ◽

Tnf Α ◽

Ifn Γ

ABSTRACT A real-time quantitative reverse transcription-PCR assay was developed for the quantification of cytokine mRNA expression in the golden Syrian hamster Mesocricetus auratus infected with Leishmania infantum and treated with amphotericin B (AMB) formulated in microspheres made of human serum albumin (HSA). Treatment was administered intravenously on days 69, 71, and 73 postinfection (p.i.) with 107 metacyclic promastigotes, at doses of 2 and 40 mg/kg of AMB. High infection levels were recorded for untreated animals by day 76 p.i., with parasite loads always about 2 log10 per gram higher in the liver than in the spleen. Treatment was highly effective with both doses, but at 40 mg/kg, almost complete parasite elimination was achieved. mRNA expression of gamma interferon (IFN-γ) and, to a lesser extent, tumor necrosis factor alpha (TNF-α) and transforming growth factor beta (TGF-β) in spleen cells was up-regulated in most animals of the untreated group. The mRNA expression of interleukin-4 was strongly down-regulated in untreated as well as treated infected animals. Treatment with the lower dose of AMB-HSA down-regulated the mRNA expression of IFN-γ and TNF-α, with no effect on the deactivating cytokine TGF-β. In contrast, treatment with the higher dose (40 mg/kg) of the formulation caused moderate up-regulation of IFN-γ and TNF-α and strong suppression of TGF-β. Treatment of noninfected animals did not alter the cytokine expression pattern with regard to untreated controls. Our results suggest that treatment of L. infantum-infected Syrian hamsters with highly effective nontoxic doses of AMB-HSA causes deactivation of the anti-inflammatory cytokine TGF-β, which in turn results in up-regulation of the Th1 cytokines IFN-γ and TNF-α.

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Temporal regulation of cytokine mRNA expression by tristetraprolin: dynamic control by p38 MAPK and MKP-1

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00219.2014 ◽

2015 ◽

Vol 308 (9) ◽

pp. L973-L980 ◽

Cited By ~ 19

Author(s):

Pavan Prabhala ◽

Kristin Bunge ◽

Md. Mostafizur Rahman ◽

Qi Ge ◽

Andrew R. Clark ◽

...

Keyword(s):

Smooth Muscle ◽

Mrna Expression ◽

P38 Mapk ◽

Airway Smooth Muscle Cells ◽

Cytokine Mrna ◽

Temporal Regulation ◽

Cytokine Mrna Expression ◽

Tnf Α ◽

Inflammatory Proteins ◽

Anti Inflammatory

Cytokines drive many inflammatory diseases, including asthma. Understanding the molecular mechanisms responsible for cytokine secretion will allow us to develop novel strategies to repress inflammation in the future. Harnessing the power of endogenous anti-inflammatory proteins is one such strategy. In this study, we investigate the p38 MAPK-mediated regulatory interaction of two anti-inflammatory proteins, mitogen-activated protein kinase phosphatase 1 (MKP-1) and tristetraprolin (TTP), in the context of asthmatic inflammation. Using primary cultures of airway smooth muscle cells in vitro, we explored the temporal regulation of IL-6 cytokine mRNA expression upon stimulation with TNF-α. Intriguingly, the temporal profile of mRNA expression was biphasic. This was not due to COX-2-derived prostanoid upregulation, increased expression of NLRP3 inflammasome components, or upregulation of the cognate receptor for TNF-α-TNFR1. Rather, the biphasic nature of TNF-α-induced IL-6 mRNA expression was regulated temporally by the RNA-destabilizing molecule, TTP. Importantly, TTP function is controlled by p38 MAPK, and our study reveals that its expression in airway smooth muscle cells is p38 MAPK-dependent and its anti-inflammatory activity is also controlled by p38 MAPK-mediated phosphorylation. MKP-1 is a MAPK deactivator; thus, by controlling p38 MAPK phosphorylation status in a temporally distinct manner, MKP-1 ensures that TTP is expressed and made functional at precisely the correct time to repress cytokine expression. Together, p38 MAPK, MKP-1, and TTP may form a regulatory network that exerts significant control on cytokine secretion in proasthmatic inflammation through precise temporal signaling.

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