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Cell Stress and Chaperones

, Volume 22, Issue 2, pp 271–291 | Cite as

Acute exercise boosts cell proliferation and the heat shock response in lymphocytes: correlation with cytokine production and extracellular-to-intracellular HSP70 ratio

  • Thiago Gomes HeckEmail author
  • Sofia Pizzato Scomazzon
  • Patrícia Renck Nunes
  • Cinthia Maria Schöler
  • Gustavo Stumpf da Silva
  • Aline Bittencourt
  • Maria Cristina Faccioni-Heuser
  • Mauricio Krause
  • Roberto Barbosa Bazotte
  • Rui Curi
  • Paulo Ivo Homem de BittencourtJrEmail author
Original Paper

Abstract

Exercise stimulates immune responses, but the appropriate “doses” for such achievements are unsettled. Conversely, in metabolic tissues, exercise improves the heat shock (HS) response, a universal cytoprotective response to proteostasis challenges that are centred on the expression of the 70-kDa family of intracellular heat shock proteins (iHSP70), which are anti-inflammatory. Concurrently, exercise triggers the export of HSP70 towards the extracellular milieu (eHSP70), where they work as pro-inflammatory cytokines. As the HS response is severely compromised in chronic degenerative diseases of inflammatory nature, we wondered whether acute exercise bouts of different intensities could alter the HS response of lymphocytes from secondary lymphoid organs and whether this would be related to immunoinflammatory responses. Adult male Wistar rats swam for 20 min at low, moderate, high or strenuous intensities as per an overload in tail base. Controls remained at rest under the same conditions. Afterwards, mesenteric lymph node lymphocytes were assessed for the potency of the HS response (42 °C for 2 h), NF-κB binding activity, mitogen-stimulated proliferation and cytokine production. Exercise stimulated cell proliferation in an “inverted-U” fashion peaking at moderate load, which was paralleled by suppression of NF-κB activation and nuclear location, and followed by enhanced HS response in relation to non-exercised animals. Comparative levels of eHSP70 to iHSP70 (H-index) matched IL-2/IL-10 ratios. We conclude that exercise, in a workload-dependent way, stimulates immunoinflammatory performance of lymphocytes of tissues far from the circulation and this is associated with H-index of stress response, which is useful to assess training status and immunosurveillance balance.

Keywords

Heat shock response HSP70 eHSP70/iHSP70 ratio HSP70 H-index Exercise Lymphocyte Immune function Inflammation 

Abbreviations

β-MCD

Methyl-β-cyclodextrin

APC

Antigen-presenting cell

BSA

Bovine serum albumin

Con A

Concanavalin A

DAB

3,3′-Diaminobenzidine tetrahydrochloride

DAPI

4′,6-Diamidino-2-phenylindole dihydrochloride

FBS

Foetal bovine serum

HIER

Heat-induced epitope retrieval

HS

Heat shock

HSF1

Heat shock transcription factor-1

HSP70

70 kDa family of heat shock proteins

eHSP70

Extracellular HSP70

iHSP70

Intracellular HSP70

HRP

Horseradish peroxidase

IEM

Immunoelectron microscopy

IF

Immunofluorescence

IHC

Immunohistochemistry

IKKs

Inhibitor of nuclear factor κB (IκB) kinases

IL

Interleukin

JNK

c-Jun N-terminal kinase

NF-κB

Nuclear transcription factors from the kappa light chain enhancer of activated B cells (κB) family

PBMC

Peripheral blood mononuclear cells

PBS

Phosphate-buffered saline

TCA

Trichloroacetic acid

TLR

Toll-like receptor

TNF-α

Tumour necrosis factor-α

Notes

Acknowledgements

TGH and CMS were supported by a fellowship from CAPES-Brasília. SPS, PRN and GSS were supported by fellowships from CNPq. The authors are grateful to Sílvia Barbosa and Christiane Lopes for technical support in sample preparation for electronic microscopy. We also appreciate the free access to the facilities of The Federal University of Rio Grande do Sul Electronic Microscopy Centre (CME/UFRGS).

Author contribution

TGH and PIHBJ designed the study. TGH, SPS, PRN and AB completed all the experiments described in this manuscript. CMS and GSS performed experiments on gene expressions. MCFH, TGH and PIHBJ designed immunoelectron microscopy analyses and MCFH blindly analysed all the samples. All authors were involved in analysing the results. TGH, CMS and PIHB supervised statistical analyses. TGH, SPS, MK and PIHBJ co-wrote the paper. PIHBJ, MK, RBB and RC provided experimental advice and helped with manuscript revision. PIHB prepared the figures, performed microscopy quantifications and revised the final version of the manuscript. All the authors had final approval of the submitted and published versions.

Compliance with ethical standards

All the procedures performed in studies involving the animals followed the ethical rules established by Arouca’s Act (Federal Law 11794/2008) and the Guide for Care and Use of Experimental Animals published by the National Institutes of Health (NIH publication no. 85-23, revised in 1996). The procedures were approved by the Federal University of Rio Grande do Sul Ethics Committee on Animal Experimentation (CEUA #2008110), according to the guidelines of the Brazilian National Council for the Control of Animal Experimentation (CONCEA).

Funding

PIHBJ and RC were responsible for grant support with respect to The Brazilian National Council for Scientific and Technological Development [CNPq, grant #563870/2010-9 to RC and grants #5510987/2007-8, 402626/2012-5, 402364/2012-0 to PIHBJ], while TGH was responsible for grant support from CNPq [#382692/2011-0] and [FAPERGS no. 002106-2551/13-5] which funded the present work.

Conflict of interest

The authors declare that they have no conflicts of interest.

Supplementary material

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Copyright information

© Cell Stress Society International 2017

Authors and Affiliations

  • Thiago Gomes Heck
    • 1
    • 2
    Email author
  • Sofia Pizzato Scomazzon
    • 2
    • 3
  • Patrícia Renck Nunes
    • 2
  • Cinthia Maria Schöler
    • 2
  • Gustavo Stumpf da Silva
    • 2
  • Aline Bittencourt
    • 2
  • Maria Cristina Faccioni-Heuser
    • 4
  • Mauricio Krause
    • 2
  • Roberto Barbosa Bazotte
    • 5
  • Rui Curi
    • 6
    • 7
  • Paulo Ivo Homem de BittencourtJr
    • 2
    Email author
  1. 1.Physiology Research Group, Department of Life Sciences, Postgraduate Program in Integral Attention to HealthRegional University of the Northwestern Rio Grande do Sul StateIjuíBrazil
  2. 2.Laboratory of Cellular Physiology, Department of Physiology, Institute of Basic Health SciencesFederal University of Rio Grande do SulPorto AlegreBrazil
  3. 3.Department of BiologyUniversity of Rome Tor VergataRomeItaly
  4. 4.Department of Morphological Sciences, Institute of Basic Health SciencesFederal University of Rio Grande do SulPorto AlegreBrazil
  5. 5.Department of Pharmacology and TherapeuticsState University of MaringáMaringáBrazil
  6. 6.Department of Physiology and Biophysics, Institute of Biomedical SciencesUniversity of São PauloSão PauloBrazil
  7. 7.Institute of Physical Activity Sciences and SportsCruzeiro do Sul UniversitySão PauloBrazil

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