Regular Voluntary Exercise Potentiates Interleukin-1β and Interleukin-18 Secretion by Increasing Caspase-1 Expression in Murine Macrophages.

Ken Shirato,Takako Kizaki,Kazuhiko Imaizumi,Takuya Sakurai,Junetsu Ogasawara,Hideki Ohno

doi:10.1155/2017/9290416

Abstract

Moderate-intensity regular exercise improves proinflammatory responses of lipopolysaccharide- (LPS-) stimulated macrophages. However, intracellular events that mediate the beneficial effects of exercise were unclear. This study aimed to clarify the mechanism by which regular voluntary exercise (VE) improves proinflammatory cytokine production by macrophages challenged with LPS. Peritoneal macrophages from VE mice secreted considerably higher amounts of interleukin- (IL-) 1β and IL-18 than did cells from sedentary control (SC) mice in the presence and absence of LPS, although tumor necrosis factor-α and IL-10 secretion were comparable between both groups. The mRNA levels of these cytokines increased significantly in response to LPS; similar levels were noted in macrophages from both SC and VE mice. Moreover, LPS evoked similar levels of degradation of inhibitor of κB (IκB) α and phosphorylation of IκB kinase β, c-Jun N-terminal kinase, and p38 in macrophages from SC and VE mice. These results indicate that the increased IL-1β and IL-18 secretion in VE mice are regulated posttranscriptionally. On the other hand, macrophages from VE mice showed higher amounts of caspase-1 protein than did cells from SC mice. These results suggest that regular VE potentiates IL-1β and IL-18 secretion in LPS-challenged macrophages by increasing caspase-1 levels.

Highlights

Macrophages play crucial roles in the first line of host defense against pathogen infection, partially by facilitating inflammation in infectious foci
We found that the mRNA levels of F4/80 and TLR4 in peritonealexudate macrophages did not significantly differ between the sedentary control (SC) and voluntary exercise (VE) mice (Figure 2), which suggested that the proportion of macrophage populations recruited into the peritoneal cavity was not affected by regular VE for 8 weeks
We aimed to determine the mechanism by which regular VE improves proinflammatory cytokine production by macrophages challenged with LPS

Summary

Introduction

Macrophages play crucial roles in the first line of host defense against pathogen infection, partially by facilitating inflammation in infectious foci. Macrophages recognize a wide variety of pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide (LPS), an outer membrane component of gram-negative bacteria, via pattern recognition receptors, including the Toll-like receptor (TLR) family of proteins [1]. TLR4 mediates LPS-induced activation of nuclear factor-κB (NF-κB) and expression of inflammatory cytokines. Processing of proinflammatory cytokines after translation influences the degree of inflammation. The regulatory machinery for interleukin- (IL-) 1β and IL18 maturation and secretion substantially differs from that for most other pro- and anti-inflammatory cytokines, such as tumor necrosis factor- (TNF-) α and IL-10 [4]. Danger-associated molecular patterns (DAMPs), for example, ATP, cholesterol crystals, urate

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