Regulation of interleukin-12 by interleukin-10, transforming growth factor-beta, tumor necrosis factor-alpha, and interferon-gamma in human monocytes infected with Mycobacterium tuberculosis H37Ra.
Regulation of interleukin (IL)-12 production by coexpression of tumor necrosis factor (TNF)-alpha, IL-10, and transforming growth factor (TGF)-beta in human monocytes infected with Mycobacterium tuberculosis H37Ra was analyzed. Also, since IL-12 induces interferon (IFN)-gamma, the effect of IFN-gamma on IL-12 expression was examined. IL-12 mRNA was measured by reverse transcriptase-polymerase chain reaction and IL-12 protein by ELISA. IL-12 p35 mRNA was constitutive and inducible. IL-12 p70 protein paralleled IL-12 p40 protein expression. TNF-alpha protein expression occurred earlier than IL-12 p40 protein but was not required for IL-12 induction. Addition or neutralization of TGF-beta did not significantly alter IL-12 induction. In contrast, recombinant IL-10 reduced IL-12 and neutralization of IL-10 minimally enhanced IL-12. A pronounced increase in IL-12 followed IFN-gamma pretreatment, which selectively up-regulated IL-12 p35 mRNA. Further understanding of operative cytokine networks during M. tuberculosis infection may improve strategies for vaccine development and immunotherapy.
Fulton
S A
SA
Division of Infectious Diseases, Case Western Reserve University, Cleveland, Ohio, USA. sxf24@po.cwru.edu
Cross
J V
JV
Toossi
Z T
ZT
Boom
W H
WH
D006133:Growth Substances / Q000096:biosynthesis*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis*; D009000:Monocytes / Q000276:immunology* / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D006133:Growth Substances; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma