Regulation of Nuclear Factor-κB and Its Inhibitor IκB-α/MAD-3 in Monocytes by Mycobacterium tuberculosis and during Human Tuberculosis

Zahra Toossi, Beverly D. Hamilton, Manijeh H. Phillips, Lynn E. Averill, Jerrold J. Ellner, Anupama Salvekar

Research output: Contribution to journalArticlepeer-review

Abstract

Blood monocytes from patients with active tuberculosis are activated in vivo, as evidenced by an increase in the stimulated release of proinflammatory cytokines, such as TNF-α, and the spontaneous expression of IL-2R. Further, monocytes from patients demonstrate an augmented susceptibility to a productive infection with HIV-1 in vitro. Mycobacterium tuberculosis and its components are strong signals to activate monocytes to production of cytokines. In this study we examined the basis of activation of monocytes during active tuberculosis and by M. tuberculosis. We found a constitutive degradation of IκB-α, the major cytoplasmic inhibitor of nuclear factor κB (NF-κB), in freshly isolated PBMC and monocytes from patients with tuberculosis. In contrast, IκB-α levels in PBMC and monocytes from healthy subjects or from patients with nontuberculous pulmonary conditions were intact. Further, by electrophoretic mobility shift assay, NF-κB was activated in monocytes from tuberculous patients. The expression of IκB-α gene, which is responsive to activation by NF-κB, was up-regulated in PBMC and monocytes from patients, but not in mononuclear cells from healthy subjects or those with nontuberculous lung diseases. By contrast, the expression of other adherence-associated early genes, such as IL-8 and IL-1β, was not up-regulated in PBMC of tuberculous patients. Further, M. tuberculosis and its tuberculin, purified protein derivative, induced the degradation of IκB-α and the expression of IκB-α mRNA, and purified protein derivative induced the activation of NF-κB in monocytes.

Original languageEnglish (US)
Pages (from-to)4109-4116
Number of pages8
JournalJournal of Immunology
Volume159
Issue number8
StatePublished - Oct 15 1997
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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