Uropathogenic Escherichia coli causes cortical tubular necrotic cell death and the release of macrophage migration inhibitory factor |
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| Authors: | Ming-Yuan Hong Chin-Chung Tseng Chia-Chang Chuang Chia-Ling Chen Yu-Huei Lin Chia-Yuan Hsieh Yu-Tzu Chang Chung-Hsi Hsing Kwang-Yu Chang Chiou-Feng Lin |
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| Affiliation: | 1. Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan;2. Department of Emergency Medicine, National Cheng Kung University Hospital, Tainan 701, Taiwan;3. Department of Internal Medicine, National Cheng Kung University Hospital, Tainan 701, Taiwan;4. Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan;5. Department of Anesthesiology, Chi Mei Medical Center, Tainan 710, Taiwan;6. National Institute of Cancer Research, National Health Research Institutes, Tainan 704, Taiwan;7. Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan;8. Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan |
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| Abstract: | The macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine, is deregulated in acute kidney injury (AKI) through an unknown mechanism. In the present study, we used a previously described mouse model of ascending urinary tract infection in which uropathogenic Escherichia coli (UPEC) were transurethrally inoculated to induce kidney infections. Here, we show that urinary MIF was upregulated during AKI while MIF was abundantly expressed in the renal cortical tubules and that UPEC infection caused a decrease in tubular MIF. Infections with UPEC in vitro caused MIF release in a cell type-dependent manner, which was independent of receptor-mediated internalization, signal transduction, and transcription. Indeed, UPEC infection-induced necrotic cell death in vitro and in vivo correlated with extracellular acidification and processed MIF secretion. These data suggest that MIF is released by necrotic renal cortical tubular cells during UPEC infection. |
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