Activation of NF-kappa B in Mycobacterium tuberculosis induced interleukin-2 receptor expression in mononuclear phagocytes

Citation
Km. Tchou-wong et al., Activation of NF-kappa B in Mycobacterium tuberculosis induced interleukin-2 receptor expression in mononuclear phagocytes, AM J R CRIT, 159(4), 1999, pp. 1323-1329
Citations number
51
Categorie Soggetti
Cardiovascular & Respiratory Systems","da verificare
Journal title
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
ISSN journal
1073449X → ACNP
Volume
159
Issue
4
Year of publication
1999
Pages
1323 - 1329
Database
ISI
SICI code
1073-449X(199904)159:4<1323:AONBIM>2.0.ZU;2-F
Abstract
Soluble interleukin-2 receptor-alpha (IL-2R alpha) has been reported to be increased in the sera of patients with advanced tuberculosis, and levels de cline after therapy in accordance with improvement of radiologic findings. We investigated expression of the IL-2R alpha in bronchoalveolar lavage (BA L) cells in active pulmonary tuberculosis, and evaluated the mechanism Myco bacterium tuberculosis induces in the IL-2R alpha using the THP-1 mononucle ar phagocyte cell line. We found IL-2R alpha expression to be increased in BAL cells from involved sites of active pulmonary tuberculosis. Expression of the alpha-chain of IL-2R alpha on peripheral blood monocytes (PBM) was i nduced by M. tuberculosis by flow cytometry evaluation. Northern analysis d emonstrated increased IL-2R alpha gene expression after stimulation with M. tuberculosis which was further induced by interferon-gamma (IFN-gamma). Th e IL-2R alpha promoter containing the nuclear factor kappa B (NF-kappa B) s ite was transcriptionally induced by M. tuberculosis and this NF-kappa B si te could confer inducibility to a heterologous herpes thymidine kinase (TK) promoter by M. tuberculosis. Electrophoretic mobility shift assays (EMSAs) revealed specific binding of nuclear protein to the NF-kappa B site upon i nduction with M. tuberculosis. Using antibodies against the p50 and p65 sub units of NF-kappa B in EMSAs, the involvement of both p50 and p65 proteins was further demonstrated. Functional expression of the IL-2R alpha on monon uclear phagocytes in M. tuberculosis infection may play an important immuno modulatory role in the host response.