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

Sci Rep. 2017 Apr 27;7(1):1214. doi: 10.1038/s41598-017-01405-z.

Abstract

Heat shock proteins (HSPs) have been shown to modulate NF-κB activation. It is unknown whether HSP70 plays a role in modulating NF-κB-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-IκBα and p65 NF-κB activities. Inhibition of NF-κB activation using NF-κB or MAPK inhibitors increased HSP70 expression in AM of TB patients. Blocking p38- or ERK-MAPK decreased NF-κB and IκB 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-κB activation in AM of TB patients, through inhibiting IκB-α phosphorylation or acting as a chaperon molecule to prevent NF-κB 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Female
  • HSP70 Heat-Shock Proteins / metabolism*
  • Humans
  • Macrophage Activation*
  • Macrophages, Alveolar / immunology*
  • Male
  • Middle Aged
  • NF-kappa B / metabolism*
  • Tuberculosis, Pulmonary / pathology*

Substances

  • HSP70 Heat-Shock Proteins
  • NF-kappa B