Nitric oxide modulates interleukin-1β and tumor necrosis factor-α synthesis by alveolar macrophages in pulmonary tuberculosis

Han Pin Kuo, Chun Hua Wang, Kuo Shiung Huang, Horng Chyuan Lin, Chih Teng Yu, Chien Yin Liu, Ling Chuan Lu

Research output: Contribution to journalArticlepeer-review

58 Citations (Scopus)

Abstract

Interleukin (IL)-1β and tumor necrosis factor (TNF)-α released from alveolar macrophages (AM) in pulmonary tuberculosis (TB) are important in host defense against mycobacterial infection. Nitric oxide (NO) production is enhanced in AM of TB patients. We examined whether NO was implicated in (IL)- 1β and TNF-α synthesis by AM of TB patients. Purified AM were retrieved by bronchoalveolar lavage from 11 TB patients and 10 normal subjects, and were cultured with or without the NO inhibitor N(G)-monomethyl-L-arginine (L- NMMA). The release of IL-1β and TNF-α, and expression of their messenger RNAs (mRNAs), were determined by enzyme-linked immunosorbent assay and Northern blot analysis. The release of IL-1β and TNF-α was greater from AM of TB patients than from AM of normal subjects. L-NMMA inhibited nitrite, IL- 1β, and TNF-α production in TB patients. The mRNA expression for IL-1β and TNF-α was upregulated in TB patients and was depressed by L-NMMA. Immunocytochemistry done with a monoclonal antibody against the p65 subunit of nuclear factor (NF)-κB showed that NF-κB was highly expressed and translocated to the nuclei of AM from TB patients, and was inhibited by L- NMMA. Inhibition of NF-κB by pyrrolidine dithiocarbamate attenuated IL-1β and TNF-α synthesis. In conclusion, enhanced NO generation by AM of TB patients plays an autoregulatory role in amplifying the synthesis of proinflammatory cytokines, probably through NF-κB activation.

Original languageEnglish
Pages (from-to)192-199
Number of pages8
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume161
Issue number1
Publication statusPublished - Jan 31 2000
Externally publishedYes

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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