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Inhibitory effects of simvastatin on staphylococcus aureus lipoteichoic acid-induced inflammation in human alveolar macrophages

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Abstract

Staphylococcus aureus (S. aureus) is the most common bacterium in sepsis and pneumonia involving gram-positive bacteria. Lipoteichoic acid (LTA) is a cell wall component of gram-positive bacteria. It is a potent inducer of inflammatory mediators in human dendritic cells, human pulmonary epithelial cells, and murine macrophages. However, the effect of LTA on human alveolar macrophages (AMs) which are the major effector cells in host defense against respiratory tract infections has hardly been studied. Statins have anti-inflammatory, immunomodulatory, antioxidative, anticoagulant, and antibacterial activities. These effects may be contributed to reduce the markers of systemic inflammation. Emerging retrospective studies have demonstrated that statin use decreased the mortality of pneumonia. However, the precise mechanisms responsible for these effects are unclear. The purpose of this study is to define the role of S. aureus LTA in human AMs and the effects of simvastatin (SV) on LTA-stimulated human AMs. The results showed that LTA induced tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), IL-8 mRNA expression, and suppressed IL-10 mRNA expression in human AMs. Simultaneously, LTA induced human AMs apoptosis. These effects were parallel with the up-regulation of the expression of NF-κB-P65 protein in the LTA-stimulated human AMs. The above effects of LTA on human AMs were inhibited significantly by SV. These data indicate that S. aureus LTA induces potent pro-inflammatory and pro-apoptotic effects on human AMs and statins exert anti-inflammatory effects by mediating inhibition of NF-κB activation and cytokine mRNA expression in human AMs. These results may explain, in part, the mechanisms responsible for favorable effects of statins on pneumonia.

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Abbreviations

AMs:

Alveolar macrophages

LTA:

Lipoteichoic acid

S. aureus :

Staphylococcus aureus

SV:

Simvastatin

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Acknowledgments

Prof. Xian Rao, Dr. Feng-Li Zhou, and Dr. Jing Huang were greatly appreciated for assisting in the collection of tissue and BAL samples. Grant support: National Science Foundation of China (No. 81170004).

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Authors and Affiliations

  1. Department of Internal Medicine, Medical Intensive Care Unit and Division of Respiratory Diseases, Institute of Respiratory Disease and the Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China

    Ben-Quan Wu, Jin-Mei Luo, Yan-Hong Wang, Yun-Feng Shi, Hui Liu, Jun-Hui Ba & Tian-Tuo Zhang

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  1. Ben-Quan Wu
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  2. Jin-Mei Luo
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Correspondence to Ben-Quan Wu.

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Ben-Quan Wu and Jin-Mei Luo contributed equally to the work and they are the co-first authors.

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Wu, BQ., Luo, JM., Wang, YH. et al. Inhibitory effects of simvastatin on staphylococcus aureus lipoteichoic acid-induced inflammation in human alveolar macrophages. Clin Exp Med 14, 151–160 (2014). https://doi.org/10.1007/s10238-013-0231-z

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  • DOI: https://doi.org/10.1007/s10238-013-0231-z

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