Inflammation-Related Genes Are Differentially Expressed in Lipopolysaccharide-Stimulated Peripheral Blood Mononuclear Cells after 3 Months of Resistance Training in Older Women
Abstract
:1. Introduction
2. Materials and Methods
2.1. Participants
2.2. Intervention
2.3. PBMC Isolation, Culture, and RNA Extraction
2.4. RNA Quality Assessment and RNA Sequencing
2.5. Statistical Analyses and Pathway Analyses
- Exercise-induced increase in upregulation following LPS stimulation, which means that the LPS stimulation upregulates the gene at baseline and after three months, and the expression is higher after the three-month exercise intervention.(Effects after three months exercise intervention > Effects baseline UP)
- Exercise-induced increase in downregulation following LPS stimulation, which means that the LPS stimulation downregulates the gene at baseline and after three months, and the expression is lower after the three-month exercise intervention.(Effects after three months exercise intervention > effects baseline DOWN)
- Exercise-induced decrease in upregulation following LPS stimulation, which means that the LPS stimulation upregulates the gene at baseline and after three months, and the expression is lower after the three-month exercise intervention.(Effects after three months exercise intervention < effects baseline UP)
- Exercise-induced decrease in downregulation following LPS stimulation, which means that the LPS stimulation downregulates the gene at baseline and after three months, and the expression is lower after the three-month exercise intervention.(Effects after three months exercise intervention < effects baseline DOWN)
- Exercise-induced change from upregulation to downregulation following LPS stimulation, which means that the LPS stimulation upregulates the gene at baseline and downregulates it after three months.(UP to DOWN)
- Exercise-induced change from downregulation to upregulation following LPS stimulation, which means that the LPS stimulation downregulates the gene at baseline and upregulates it after three months.(DOWN to UP)
3. Results
3.1. Baseline
3.2. Exercise-Induced Gene Expression Changes in Post-Cultured LPS-Stimulated PBMCs
3.2.1. Exercise-Induced Increase in Upregulation or Downregulation (Enhanced Effects)
3.2.2. Exercise-Induced Decrease in Upregulation and Downregulation (Attenuated Effects)
3.2.3. Exercise-Induced Changes in Down- or Upregulation (Changed Effects)
3.2.4. Exercise-Induced Upregulated Effects vs. Exercise-Induced Downregulated Effects
3.3. Pathway Analyses
4. Discussion
4.1. Exercise-Induced Effects
4.1.1. Pattern Recognition Receptors (PRRs)
4.1.2. Interleukins and Interferons
4.1.3. Chemokines and Tumor Necrosis Family
4.1.4. Genes Related to the NF-KB Pathway
4.1.5. Other Inflammation-Related Genes
4.2. Pathway Analyses Findings
4.3. Strengths and Limitations
4.4. Future Perspectives
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Krabbe, K.; Pedersen, M.; Bruunsgaard, H. Inflammatory mediators in the elderly. Exp. Gerontol. 2004, 39, 687–699. [Google Scholar] [CrossRef] [PubMed]
- Gabay, C.; Kushner, I. Acute-phase proteins and other systemic responses to inflammation. N. Engl. J. Med. 1999, 340, 448–454. [Google Scholar] [CrossRef] [PubMed]
- Bruunsgaard, H.; Skinhoj, P.; Qvist, J.; Pedersen, B.K. Elderly humans show prolonged in vivo inflammatory activity during pneumococcal infections. J. Infect. Dis. 1999, 180, 551–554. [Google Scholar] [CrossRef]
- Petersen, A.M.; Pedersen, B.K. The anti-inflammatory effect of exercise. J. Appl. Physiol. 2005, 98, 1154–1162. [Google Scholar] [CrossRef]
- Bautmans, I.; Njemini, R.; Vasseur, S.; Chabert, H.; Moens, L.; Demanet, C.; Mets, T. Biochemical changes in response to intensive resistance exercise training in the elderly. Gerontology 2005, 51, 253–265. [Google Scholar] [CrossRef]
- Fischer, C.P. Interleukin-6 in acute exercise and training: What is the biological relevance? Exerc. Immunol. Rev. 2006, 12, 6–33. [Google Scholar]
- Teissier, T.; Boulanger, E.; Cox, L.S. Interconnections between Inflammageing and Immunosenescence during Ageing. Cells 2022, 11, 359. [Google Scholar] [CrossRef]
- Abbasi, A.; Hauth, M.; Walter, M.; Hudemann, J.; Wank, V.; Niess, A.M.; Northoff, H. Exhaustive exercise modifies different gene expression profiles and pathways in LPS-stimulated and un-stimulated whole blood cultures. Brain Behav. Immun. 2014, 39, 130–141. [Google Scholar] [CrossRef]
- Stewart, L.K.; Flynn, M.G.; Campbell, W.W.; Craig, B.A.; Robinson, J.P.; McFarlin, B.K.; Timmerman, K.L.; Coen, P.M.; Felker, J.; Talbert, E. Influence of exercise training and age on CD14+ cell-surface expression of toll-like receptor 2 and 4. Brain Behav. Immun. 2005, 19, 389–397. [Google Scholar] [CrossRef]
- Simpson, R.J. Aging, persistent viral infections, and immunosenescence: Can exercise “make space”? Exerc. Sport. Sci. Rev. 2011, 39, 23–33. [Google Scholar] [CrossRef] [PubMed]
- Simpson, R.J.; Guy, K. Coupling aging immunity with a sedentary lifestyle: Has the damage already been done?—A mini-review. Gerontology 2010, 56, 449–458. [Google Scholar] [CrossRef] [PubMed]
- Liberman, K.; Njemini, R.; Forti, L.N.; Cools, W.; Debacq-Chainiaux, F.; Kooijman, R.; Beyer, I.; Bautmans, I. Three months of strength training changes the gene expression of inflammation-related genes in PBMC of older women: A randomized controlled trial. Cells 2022, 11, 531. [Google Scholar] [CrossRef] [PubMed]
- Folstein, M.F.; Folstein, S.E.; McHugh, P.R. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J. Psychiatr. Res. 1975, 12, 189–198. [Google Scholar] [CrossRef]
- Dipietro, L.; Caspersen, C.J.; Ostfeld, A.M.; Nadel, E.R. A survey for assessing physical activity among older adults. Med. Sci. Sports Exerc. 1993, 25, 628–642. [Google Scholar] [CrossRef]
- Faul, F.; Erdfelder, E.; Buchner, A.; Lang, A.G. Statistical power analyses using G*Power 3.1: Tests for correlation and regression analyses. Behav. Res. Methods 2009, 41, 1149–1160. [Google Scholar] [CrossRef]
- Love, M.I.; Huber, W.; Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014, 15, 550. [Google Scholar] [CrossRef]
- Olesen, J.; Biensø, R.S.; Meinertz, S.; van Hauen, L.; Rasmussen, S.M.; Gliemann, L.; Plomgaard, P.; Pilegaard, H. Impact of training status on LPS-induced acute inflammation in humans. J. Appl. Physiol. 2015, 118, 818–829. [Google Scholar] [CrossRef] [PubMed]
- Fernandez-Gonzalo, R.; De Paz, J.A.; Rodriguez-Miguelez, P.; Cuevas, M.J.; González-Gallego, J. Effects of eccentric exercise on toll-like receptor 4 signaling pathway in peripheral blood mononuclear cells. J. Appl. Physiol. 2012, 112, 2011–2018. [Google Scholar] [CrossRef] [PubMed]
- Abbasi, A.; Fehrenbach, E.; Hauth, M.; Walter, M.; Hudemann, J.; Wank, V.; Niess, A.M.; Northoff, H. Changes in spontaneous and LPS-induced ex vivo cytokine production and mRNA expression in male and female athletes following prolonged exhaustive exercise. Exerc. Immunol. Rev. 2013, 19, 28. [Google Scholar]
- Ulven, S.M.; Foss, S.S.; Skjølsvik, A.M.; Stadheim, H.K.; Myhrstad, M.C.; Raael, E.; Sandvik, M.; Narverud, I.; Andersen, L.F.; Jensen, J. An acute bout of exercise modulate the inflammatory response in peripheral blood mononuclear cells in healthy young men. Arch. Physiol. Biochem. 2015, 121, 41–49. [Google Scholar] [CrossRef]
- Ramesh, G.; MacLean, A.G.; Philipp, M.T. Cytokines and chemokines at the crossroads of neuroinflammation, neurodegeneration, and neuropathic pain. Mediat. Inflamm. 2013, 2013, 480739. [Google Scholar] [CrossRef]
- Bazan, J.F.; Bacon, K.B.; Hardiman, G.; Wang, W.; Soo, K.; Rossi, D.; Greaves, D.R.; Zlotnik, A.; Schall, T.J. A new class of membrane-bound chemokine with a CX3C motif. Nature 1997, 385, 640–644. [Google Scholar] [CrossRef]
- Gjevestad, G.O.; Holven, K.B.; Ulven, S.M. Effects of exercise on gene expression of inflammatory markers in human peripheral blood cells: A systematic review. Curr. Cardiovasc. Risk Rep. 2015, 9, 1–17. [Google Scholar] [CrossRef] [PubMed]
- Ferrucci, L.; Fabbri, E. Inflammageing: Chronic inflammation in ageing, cardiovascular disease, and frailty. Nat. Rev. Cardiol. 2018, 15, 505–522. [Google Scholar] [CrossRef]
- Puts, S.; Liberman, K.; Leysen, L.; Forti, L.; Muyldermans, E.; Vaes, P.; Nijs, J.; Beckwee, D.; Bautmans, I. Exercise-induced effects on inflammatory markers and brain-derived neurotrophic factor in patients with knee osteoarthritis. A Syst. Rev. Meta-Anal. Exerc. Immunol. Rev. 2023, 29, 22–53. [Google Scholar]
- Yarrow, J.F.; White, L.J.; McCoy, S.C.; Borst, S.E. Training augments resistance exercise induced elevation of circulating brain derived neurotrophic factor (BDNF). Neurosci. Lett. 2010, 479, 161–165. [Google Scholar] [CrossRef]
- Church, D.D.; Hoffman, J.R.; Mangine, G.T.; Jajtner, A.R.; Townsend, J.R.; Beyer, K.S.; Wang, R.; La Monica, M.B.; Fukuda, D.H.; Stout, J.R. Comparison of high-intensity vs. high-volume resistance training on the BDNF response to exercise. J. Appl. Physiol. 2016, 121, 123–128. [Google Scholar] [CrossRef] [PubMed]
- Beenakker, K.G.M.; Westendorp, R.G.J.; de Craen, A.J.M.; Chen, S.; Raz, Y.; Ballieux, B.; Nelissen, R.; Later, A.F.L.; Huizinga, T.W.; Slagboom, P.E.; et al. Men Have a Stronger Monocyte-Derived Cytokine Production Response upon Stimulation with the Gram-Negative Stimulus Lipopolysaccharide than Women: A Pooled Analysis Including 15 Study Populations. J. Innate Immun. 2020, 12, 142–153. [Google Scholar] [CrossRef] [PubMed]
- Ficarra, S.; Thomas, E.; Bianco, A.; Gentile, A.; Thaller, P.; Grassadonio, F.; Papakonstantinou, S.; Schulz, T.; Olson, N.; Martin, A.; et al. Impact of exercise interventions on physical fitness in breast cancer patients and survivors: A systematic review. Breast Cancer 2022, 29, 402–418. [Google Scholar] [CrossRef] [PubMed]
- Zhu, C.; Ma, H.; He, A.; Li, Y.; He, C.; Xia, Y. Exercise in cancer prevention and anticancer therapy: Efficacy, molecular mechanisms and clinical information. Cancer Lett. 2022, 544, 215814. [Google Scholar] [CrossRef]
- Zunner, B.E.M.; Wachsmuth, N.B.; Eckstein, M.L.; Scherl, L.; Schierbauer, J.R.; Haupt, S.; Stumpf, C.; Reusch, L.; Moser, O. Myokines and Resistance Training: A Narrative Review. Int. J. Mol. Sci. 2022, 23, 3501. [Google Scholar] [CrossRef]
- Song, Y.; Ren, F.; Sun, D.; Wang, M.; Baker, J.S.; István, B.; Gu, Y. Benefits of Exercise on Influenza or Pneumonia in Older Adults: A Systematic Review. Int. J. Environ. Res. Public Health 2020, 17, 2655. [Google Scholar] [CrossRef]
IST (n = 4) | SET (n = 5) | CON (n = 5) | p-Value | |
---|---|---|---|---|
Weight (kg) | 62.62 ± 5.41 | 69.43 ± 12.52 | 64.17 ± 4.60 | 0.47 |
Height (m) | 1.63 ± 0.05 | 1.59 ± 0.06 | 1.54 ± 0.06 | 0.11 |
BMI (kg/m2) | 23.34 ± 1.86 | 28.50 ± 3.72 | 27.44 ± 3.93 | 0.11 |
Age (years) | 70.09 ± 4.64 | 72.13 ± 5.39 | 69.45 ± 2.62 | 0.61 |
MMSE (score: 0–30) | 30.00 ± 0.00 | 27.2 ± 2.95 | 29.20 ± 0.84 | 0.10 |
Health categories (n) | ||||
A | 0 | 1 | 0 | 0.62 |
B | 4 | 3 | 5 | |
C | 0 | 1 | 0 | |
Charlson Index | 0.50 ± 1.00 | 0.00 ± 0.00 | 0.40 ± 0.89 | 0.58 |
White blood cells (%) | 0.99 (0.98–0.99) | 0.99 (0.96–0.99) | 0.99 (0.98–0.99) | 0.87 |
Monocytes (%) | 8.38 (7.91–10.08) † | 5.45 (4.70–6.88) | 7.81 (5.58–8.00) | 0.02 |
Eosinophils (%) | 1.43 (0.60–1.98) | 2.77 (0.79–4.01) | 3.99 (1.81–5.38) | 0.19 |
Basophils (%) | 0.37 (0.27–0.50) | 0.58 (0.39–0.80) | 0.79 (0.56–1.41) | 0.05 |
Lymphocytes (%) | 26.05 (21.65–38.02) | 29.40 (26.90–33.20) | 28.7 (24.20–43.62) | 0.73 |
Energy expenditure (kilocalories/week) | 6392.5 ± 2447.56 | 3520.9 ± 2509.21 | 6339.5 ± 1770.16 | 0.12 |
YPAS-ADS (Score 0–177) | 44.75 ± 9.18 | 32.00 ± 15.26 | 38.00 ± 27.29 | 0.63 |
Medication use (n) | 4.25 (0–10) | 1.20 (0–4) | 4.40 (1–7) | 0.39 |
Hypertension (n) | 0 | 1 | 2 | 0.35 |
Diabetes (n) | 0 | 0 | 0 | 1.00 |
IST | SET | CON | |
---|---|---|---|
Exercise compliance (%) | 69.96 ± 19.47 | 93.41 ± 18.86 | 80.98 ± 7.31 |
MSI baseline | 24.3 ± 6.1 kg | 34.5 ± 8.7 kg | 37.6 ± 14.5 kg |
MSI 3 months | 33.1 ± 8.5 kg | 45.7 ± 7.9 kg | 34.2 ± 4.9 kg |
p value | 0.005 * | 0.002 * | 0.54 |
Canonical Pathways | IST | SET | CON |
---|---|---|---|
Apelin cardiac fibroblast signaling pathway | 2.00 | 0.00 | −2.00 |
Cytotoxic T lymphocyte-mediated apoptosis of target cells | −2.12 | 2.83 | 0.00 |
Intrinsic prothrombin activation pathway | 2.45 | 1.34 | 0.00 |
VDR/RXR activation | 2.33 | −0.33 | 1.00 |
Apelin liver signaling pathway | 2.24 | 0.82 | −0.45 |
Role of RIG1-like receptors in antiviral innate immunity | 2.24 | −0.45 | 0.45 |
TWEAK signaling | 2.24 | −0.45 | 0.45 |
CD27 signaling in lymphocytes | 2.12 | 0.00 | −0.71 |
Leukocyte extravasation signaling | −3.15 | −0.73 | 1.70 |
IL-9 signaling | 0.30 | 2.89 | 0.91 |
IL-2 signaling | −1.73 | 2.31 | −0.58 |
Tumoricidal function of hepatic natural killer cells | −1.34 | 2.24 | −0.45 |
JAK/stat signaling | −0.23 | 2.07 | 0.23 |
Endocannabinoid neuronal synapse pathway | −1.00 | −2.00 | 0.00 |
GPCR-mediated nutrient sensing in enteroendocrine cells | −0.30 | −2.11 | −0.30 |
Neuropathic pain signaling in dorsal horn neurons | −0.30 | −2.11 | −0.30 |
AMPK signaling | −1.00 | −2.12 | 0.00 |
Apelin cardiomyocyte signaling pathway | 0.00 | −2.14 | −0.54 |
GNRH signaling | −1.16 | −2.31 | −1.73 |
Unfolded protein response | 1.16 | −2.31 | −0.58 |
Dopamine-DARPP32 feedback in cAMP signaling | −0.33 | −2.33 | −0.33 |
Cardiac hypertrophy signaling | −1.96 | −2.40 | 0.22 |
Inhibition of angiogenesis by TSP1 | 0.33 | −3.00 | −0.33 |
Crosstalk between dendritic cells and natural killer cells | 1.89 | 1.67 | 2.65 |
Neuroinflammation signaling pathway | 0.86 | −0.61 | 2.32 |
Systemic lupus erythematosus In B cell signaling pathway | 0.58 | 1.57 | 2.31 |
Th17 activation pathway | −0.20 | 1.40 | 2.20 |
T cell exhaustion signaling pathway | −0.58 | 0.96 | 2.12 |
TREM1 signaling | 0.19 | 0.37 | 2.04 |
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Salimans, L.; Liberman, K.; Cools, W.; Njemini, R.; Debacq-Chainiaux, F.; Forti, L.N.; De Dobbeleer, L.; Kooijman, R.; Beyer, I.; Bautmans, I. Inflammation-Related Genes Are Differentially Expressed in Lipopolysaccharide-Stimulated Peripheral Blood Mononuclear Cells after 3 Months of Resistance Training in Older Women. Cells 2024, 13, 1416. https://doi.org/10.3390/cells13171416
Salimans L, Liberman K, Cools W, Njemini R, Debacq-Chainiaux F, Forti LN, De Dobbeleer L, Kooijman R, Beyer I, Bautmans I. Inflammation-Related Genes Are Differentially Expressed in Lipopolysaccharide-Stimulated Peripheral Blood Mononuclear Cells after 3 Months of Resistance Training in Older Women. Cells. 2024; 13(17):1416. https://doi.org/10.3390/cells13171416
Chicago/Turabian StyleSalimans, Lene, Keliane Liberman, Wilfried Cools, Rose Njemini, Florence Debacq-Chainiaux, Louis Nuvagah Forti, Liza De Dobbeleer, Ron Kooijman, Ingo Beyer, and Ivan Bautmans. 2024. "Inflammation-Related Genes Are Differentially Expressed in Lipopolysaccharide-Stimulated Peripheral Blood Mononuclear Cells after 3 Months of Resistance Training in Older Women" Cells 13, no. 17: 1416. https://doi.org/10.3390/cells13171416