J Bacteriol Virol.  2002 Dec;32(4):401-410.

Identification and Functional Characterization of Differentially Expressed Genes in Human-derived Monocytic Cell Line U937 Infected with Mycobacterium tuberculosis H37Rv and Mycobacterium marinum: Comparative Evaluation of IL-8

• Song CH
• Lee JS
• Kim HJ
• Park JK
• Paik TH
• Jo EK

Abstract

Although Mycobacterium marinum is closely related to M. tuberculosis H37Rv (M. tbc) genomically, clinical outcome of human infection is quite different. The role of the host macrophage in determining differential pathologic responses was analyzed using an in vitro model of macrophage infection. By using subtractive hybridization, thirty-two differentially expressed genes were identified in the monocytic cell line U937 infected with M. tbc or M. marinum. Among them, IL-8 mRNA expression was more prominent in the M. tbc-infected U937 cells by Northern hybridization than in those infected with M. marinum. The IL-8 production was significantly lower in M. marinum-infected U937 or monocytes when compared with those infected by other strains of mycobacteria, such as M. tuberculosis H37Ra, M. bovis BCG or M. smegmatis. To identify possible mechanisms underlying these differences, changes in the expression of molecules such as nuclear factor-kappaB (NF-kappaB) involved in the signaling pathway activated by mycobacteria were assessed. U937 cells infected with M. tbc showed a significant degradation of IkBa proteins compared with M. marinum-infected U937 cells. Collectively, these results implicate distinct differences in IL-8 production in human macrophages infected with M. tbc or M. marinum, and suggest important role of IL-8 in the immunopathogenesis of tuberculosis.

Keyword

Subtractive hybridization; Monocyte; IL-8; M. tuberculosis; M. marinum; U937; Immunopathogenesis; Inhibitory protein IkBa

MeSH Terms

Cell Line*
Humans
Interleukin-8*
Macrophages
Monocytes
Mycobacterium bovis
Mycobacterium marinum*
Mycobacterium tuberculosis*
Mycobacterium*
RNA, Messenger
Tuberculosis
U937 Cells
Interleukin-8
RNA, Messenger