Requirement of A1-α for bacillus Calmette-Guérin-mediated protection of macrophages against nitric oxide-induced apoptosis

S. Kausalya, R. Somogyi, A. Orlofsky, Michael B. Prystowsky

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Abstract

The role of apoptosis in regulating the course of intracellular microbial infection is not well understood. We studied the relationship between apoptotic regulation and bacillus Calmette-Guérin (BCG) treatment in murine peritoneal exudate macrophages (PEM) and the J774 macrophage cell line. In both PEM and J774 cells, mRNA expression of the anti-apoptotic gene, A1, was selectively induced by BCG treatment as compared with other bcl2 family members (bcl-w, bcl-2, bcl-xl, bcl-xs, bax, bak, bad). In PEM, A1 expression was maximal by 8 h postinfection and was abrogated by the proteasomal inhibitor MG-132. The induction was independent of protein synthesis as well as the p38 mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways and did not require live organism. Three genes encoding closely related isoforms of A1 were all expressed; however, the A1-a isoform displayed the greatest fold induction in PEM. BCG-induced A1 expression was associated with protection of host macrophages from NO-mediated apoptosis in both PEM and J774 cells. BCG-mediated protection was abrogated in PEM derived from A1-a-/- mice, indicating a requirement of A1-a for survival of inflammatory macrophages.

Original languageEnglish (US)
Pages (from-to)4721-4727
Number of pages7
JournalJournal of Immunology
Volume166
Issue number7
StatePublished - Apr 1 2001

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Peritoneal Macrophages
Exudates and Transudates
Bacillus
Nitric Oxide
Macrophages
Apoptosis
Protein Isoforms
Phosphatidylinositol 3-Kinase
p38 Mitogen-Activated Protein Kinases
Genes
Cell Line
Messenger RNA
Infection
Proteins

ASJC Scopus subject areas

  • Immunology

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Requirement of A1-α for bacillus Calmette-Guérin-mediated protection of macrophages against nitric oxide-induced apoptosis. / Kausalya, S.; Somogyi, R.; Orlofsky, A.; Prystowsky, Michael B.

In: Journal of Immunology, Vol. 166, No. 7, 01.04.2001, p. 4721-4727.

Research output: Contribution to journalArticle

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