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

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.

High-intensity interval training in allogeneic adoptive T-cell immunotherapy – a big HIT?

“…Different types of stress, one of which is exercise, induces HSP70 expression in order to adapt organisms appropriately [62,63]. In a rat model, it was shown that at a high-intensity workload, HSP70 increases while the proliferation response decreases [62]. This corresponds to our findings concerning HSP70 and the proliferation marker Ki67.…”

“…Another interesting trend could be seen with HSP70. Different types of stress, one of which is exercise, induces HSP70 expression in order to adapt organisms appropriately [62,63]. In a rat model, it was shown that at a high-intensity workload, HSP70 increases while the proliferation response decreases [62].…”

Resistance training and L-arginine supplementation are determinant in genomic stability, cardiac contractility and muscle mass development in rats

“…Also, L-arginine consumption induces an increase in eHSP70 levels in serum of rats after acute exercise [ 15 , 37 , 38 ]. Generally, the release of eHSP72 from cells and tissues to bloodstream denotes a cell signaling, and usually is strongly related to danger signals from immune cells to whole body [ 17 , 39 , 40 ]. In this way, since intracellularly HSP70 has chaperone action, the eHSP72 can be considered a chaperokine in the circulation, being a cytokine-like signal [ 41 ].…”

“…The use of L-arginine supplements in animal models of exhaustive exercise training has shown increases in antioxidant defense in liver and muscles [ 13 , 14 ], and these effects were accompanied by cytoprotective expressions of 70 kDa heat shock proteins (HSP70) in both cell cytoplasm and nuclei [ 15 ]. Exercise-induced HSP70 expression in immune cells, and the release of these proteins from immune cells to the blood (in the extracellular milieu named as eHSP70), has also been found to be related to oxidative stress and inflammation in immune cells [ 16 , 17 ].…”

Fine Particulate Matter (PM2.5) Air Pollution and Type 2 Diabetes Mellitus (T2DM): When Experimental Data Explains Epidemiological Facts

“…On the other hand, increased levels of eHSP70 chronically may be a result of chronic low-grade inflammatory state of visceral obesity [39]. Therefore, the unbalance between eHSP70 and iHSP70 levels (eHSP70/iHSP70 ratio), known as H-index, can reveal the full context of inflammatory process and insulin resistance state [16,40].…”