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- CXCL12/CXCR4 Axis is Involved in the Recruitment of NK Cells by HMGB1 Contributing to Persistent Airway Inflammation and AHR During the Late Stage of RSV Infection
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Sisi Chen , Wei Tang , Guangyuan Yu , Zhengzhen Tang , Enmei Liu
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J. Microbiol. 2023;61(4):461-469. Published online February 13, 2023
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DOI: https://doi.org/10.1007/s12275-023-00018-8
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Abstract
- We previously showed that both high-mobility group box-1 (HMGB1) and natural killer (NK) cells contribute to respiratory
syncytial virus (RSV)-induced persistent airway inflammation and airway hyperresponsiveness (AHR). Meanwhile,
Chemokine (C-X-C motif) ligand 12 (CXCL12) and its specific receptor (chemokine receptor 4, CXCR4) play important
roles in recruitment of immune cells. CXCL12 has been reported to form a complex with HMGB1 that binds to CXCR4 and
increases inflammatory cell migration. The relationship between HMGB1, NK cells and chemokines in RSV-infected model
remains unclear. An anti-HMGB1 neutralizing antibody and inhibitor of CXCR4 (AMD3100) was administered to observe
changes of NK cells and airway disorders in nude mice and BALB/c mice. Results showed that the mRNA expression and
protein levels of HMGB1 were elevated in late stage of RSV infection and persistent airway inflammation and AHR were
diminished after administration of anti-HMGB1 antibodies, with an associated significant decrease in CXCR4+
NK cells. In
addition, CXCL12 and CXCR4 were reduced after HMGB1 blockade. Treatment with AMD3100 significantly suppressed
the recruitment of NK cells and alleviated the airway disorders. Thus, CXCL12/CXCR4 axis is involved in the recruitment
of NK cells by HMGB1, contributing to persistent airway inflammation and AHR during the late stage of RSV infection.
- Regulation of iron homeostasis by peroxide-sensitive CatR, a Fur-family regulator in Streptomyces coelicolor
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Yeonbum Kim , Jung-Hye Roe , Joo-Hong Park , Yong-Joon Cho , Kang-Lok Lee
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J. Microbiol. 2021;59(12):1083-1091. Published online December 4, 2021
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DOI: https://doi.org/10.1007/s12275-021-1457-1
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Abstract
- CatR, a peroxide-sensing transcriptional repressor of Fur
family, can de-repress the transcription of the catA gene encoding
catalase upon peroxide stress in Streptomyces coelicolor.
Since CatR-regulated genes other than catA and its own
gene catR have not been identified in detail, the understanding
of the role of CatR regulon is very limited. In this study,
we performed transcriptomic analysis to identify genes influenced
by both atR mutation and hydrogen peroxide treatment.
Through ChIP-qPCR and other analyses, a new consensus
sequence was found in CatR-responsive promoter region
of catR gene and catA operon for direct regulation. In
addition, vtlA (SCO2027) and SCO4983 were identified as new
members of the CatR regulon. Expression levels of iron uptake
genes were reduced by hydrogen peroxide and a DmdR1 binding
sequence was identified in promoters of these genes. The
increase in free iron by hydrogen peroxide was thought to
suppress the iron import system by DmdR1. A putative exporter
protein VtlA regulated by CatR appeared to reduce intracellular
iron to prevent oxidative stress. The name vtlA
(VIT1-like transporter) was proposed for iron homeostasis
related gene SCO2027.
Published Erratum
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