Heat shock protein70 is implicated in modulating NF-κ B activation in alveolar macrophages of patients with active pulmonary tuberculosis

Chun Hua Wang, Pai Chien Chou, Fu Tsai Chung, Horng Chyuan Lin, Kuo Hsiung Huang, Han Pin Kuo

Research output: Contribution to journalArticle

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Abstract

Heat shock proteins (HSPs) have been shown to modulate NF-κ B activation. It is unknown whether HSP70 plays a role in modulating NF-κ B-mediated pro-inflammatory cytokines released from alveolar macrophage (AM) of patients with active pulmonary tuberculosis (TB). Peripheral blood monocytes (PBMs) and AM were sampled from nineteen active TB patients and 14 healthy individuals. HSP70 expression was 3-fold higher in AMs of active TB patients than normal subjects, and declined after receiving 3-month anti-TB treatment. Overexpression of HSP70 by transfection with HSP70 plasmid decreased p-Iκ Bα and p65 NF-κ B activities. Inhibition of NF-κ B activation using NF-κ B or MAPK inhibitors increased HSP70 expression in AM of TB patients. Blocking p38- or ERK-MAPK decreased NF-κ B and Iκ B activities, leading to up-regulated HSP70 expression. Overexpression of HSP70 alone or with p38 or ERK inhibitors decreased TNF-α (57%, 83% and 74%, respectively) and IL-6 (53%, 70%, and 67%, respectively) release from macrophages of TB patients. In conclusion, HSP70 modulates NF-κ B activation in AM of TB patients, through inhibiting Iκ B-α phosphorylation or acting as a chaperon molecule to prevent NF-κ B binding to the target genes by facilitating degradation. The upregulated HSP70 may suppress the release of pro-inflammatory cytokines during active PTB infection, and prevent overwhelming tissue damage.

Original languageEnglish
Article number1214
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - Dec 1 2017

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Alveolar Macrophages
Pulmonary Tuberculosis
Shock
Tuberculosis
Hot Temperature
Cytokines
Heat-Shock Proteins
Transfection
Monocytes
Interleukin-6
Plasmids
Macrophages
Phosphorylation
Infection
Genes

ASJC Scopus subject areas

  • General

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Heat shock protein70 is implicated in modulating NF-κ B activation in alveolar macrophages of patients with active pulmonary tuberculosis. / Wang, Chun Hua; Chou, Pai Chien; Chung, Fu Tsai; Lin, Horng Chyuan; Huang, Kuo Hsiung; Kuo, Han Pin.

In: Scientific Reports, Vol. 7, No. 1, 1214, 01.12.2017.

Research output: Contribution to journalArticle

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abstract = "Heat shock proteins (HSPs) have been shown to modulate NF-κ B activation. It is unknown whether HSP70 plays a role in modulating NF-κ B-mediated pro-inflammatory cytokines released from alveolar macrophage (AM) of patients with active pulmonary tuberculosis (TB). Peripheral blood monocytes (PBMs) and AM were sampled from nineteen active TB patients and 14 healthy individuals. HSP70 expression was 3-fold higher in AMs of active TB patients than normal subjects, and declined after receiving 3-month anti-TB treatment. Overexpression of HSP70 by transfection with HSP70 plasmid decreased p-Iκ Bα and p65 NF-κ B activities. Inhibition of NF-κ B activation using NF-κ B or MAPK inhibitors increased HSP70 expression in AM of TB patients. Blocking p38- or ERK-MAPK decreased NF-κ B and Iκ B activities, leading to up-regulated HSP70 expression. Overexpression of HSP70 alone or with p38 or ERK inhibitors decreased TNF-α (57{\%}, 83{\%} and 74{\%}, respectively) and IL-6 (53{\%}, 70{\%}, and 67{\%}, respectively) release from macrophages of TB patients. In conclusion, HSP70 modulates NF-κ B activation in AM of TB patients, through inhibiting Iκ B-α phosphorylation or acting as a chaperon molecule to prevent NF-κ B binding to the target genes by facilitating degradation. The upregulated HSP70 may suppress the release of pro-inflammatory cytokines during active PTB infection, and prevent overwhelming tissue damage.",
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