Characterization of IFN-γ regulation of the complement factor B gene in macrophages

Huang, Yong; Krein, Peter M.; Winston, Brent W.

doi:10.1002/1521-4141(200112)31:12<3676::aid-immu3676>3.0.co;2-k

Cited by 27 publications

(37 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IFN-␥, IL-6-type cytokines, IL-1-type cytokines, hormones, LPS, and C5a have all been reported to effect complement expression both in vivo and by cultured cells (14,15,24,27,35,36,40,52). Detailed analyses of promoters and enhancers for factor B and C3 have demonstrated the intricate control by individual cytokines through specific regulatory sequences (21,22,23,50). Important future studies will be to define the mechanism by which factor B and C5 expression are modulated during LPS-induced lung injury.…”

Section: Discussionmentioning

confidence: 99%

Complement levels and activity in the normal and LPS-injured lung

Bolger

Ross

Jiang

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

Complement, a complex protein system, plays an essential role in host defense through bacterial lysis, stimulation of phagocytosis, recruitment of immune cells to infected tissue, and promotion of the inflammatory response. Although complement is most well-characterized in serum, complement activity is also present in the lung. Here we further characterize the complement system in the normal and inflamed lung. By Western blot, C5, C6, and factor I were detected in bronchoalveolar lavage (BAL) at lower levels than in serum, whereas C2 was detected at similar levels in BAL and serum. C4 binding protein (C4BP) was not detectable in BAL. Exposure to lipopolysaccharide (LPS) elevated levels of C1q, factor B, C2, C4, C5, C6, and C3 in human BAL and C3, C5, and factor B in mouse and rat BAL. Message for C1q-B, C1r, C1s, C2, C4, C3, C5, C6, factor B, and factor H, but not C9 or C4BP, was readily detectable by RT-PCR in normal mouse lung. Exposure to LPS enhanced factor B expression, decreased C5 expression, and did not affect C1q-B expression in mouse and rat lung. BAL from rats exposed to LPS had a greater ability to deposit C3b onto bacteria through complement activation than did BAL from control rats. In summary, these data demonstrate that complement levels, expression, and function are altered in acute lung injury and suggest that complement within the lung is regulated to promote opsonization of pathogens and limit potentially harmful inflammation.

show abstract

Section: Discussionmentioning

confidence: 99%

Complement levels and activity in the normal and LPS-injured lung

Bolger

Ross

Jiang

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

show abstract

“…Although Bf is primarily synthesized by the liver (15)(16)(17), it has also been shown to be produced at low levels by a wide variety of extrahepatic cells, including macrophage/monocytes (18,19), fibroblasts (20), epithelial cells, and endothelial cells (21,22). Macrophages are an important extrahepatic site of Bf synthesis (15,18,23,24) which may contribute significantly to the local concentration of Bf at sites of inflammation (24).…”

Section: Omplement Factor B (Bf)mentioning

confidence: 99%

Complement Factor B Gene Regulation: Synergistic Effects of TNF-α and IFN-γ in Macrophages

Huang

Krein

Muruve

et al. 2002

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Complement factor B (Bf) plays an important role in activating the alternative complement pathway. The inflammatory cytokines, in particular TNF-α and IFN-γ, are critical in the regulation of Bf gene expression in macrophages. In this study, we investigated the mechanisms of Bf gene regulation by TNF-α and IFN-γ in murine macrophages. Northern analysis revealed that Bf mRNA expression was synergistically up-regulated by TNF-α and IFN-γ in MH-S cells. Truncations of the 5′ Bf promoter identified a region between −556 and −282 bp that mediated TNF-α responsiveness as well as the synergistic effect of TNF-α and IFN-γ on Bf expression. Site-directed mutagenesis of a NF-κB-binding element in this region (−433 to −423 bp) abrogated TNF-α responsiveness and decreased the synergistic effect of TNF-α and IFN-γ on Bf expression. EMSAs revealed nuclear protein binding to this NF-κB cis-binding element on TNF-α stimulation. Supershift analysis revealed that both p50 and p65 proteins contribute to induction of Bf by TNF-α. An I-κB dominant negative mutant blocked Bf induction by TNF-α and reduced the synergistic induction by TNF-α and IFN-γ. In addition, the proteasome inhibitor MG132, which blocks NF-κB induction, blocked TNF-α-induced Bf promoter activity and the synergistic induction of Bf promoter activity by TNF-α and IFN-γ. LPS was found to induce Bf promoter activity through the same NF-κB cis-binding site. These findings suggest that a NF-κB cis-binding site between −433 and −423 bp is required for TNF-α responsiveness and for TNF-α- and IFN-γ-stimulated synergistic responsiveness of the Bf gene.

show abstract

“…IFN-␥ and IL-12 are critical for producing adequate antimicrobial responses during innate immunity. Specifically, NK cell-derived IFN-␥ activates neutrophils and macrophages, induces production of phagocytic reactive oxygen species, and is involved in activation of the alternative complement cascade (19,42,52). The critical role of NK cell-derived IFN-␥ has been demonstrated in mice that have been either genetically or transiently depleted of NK cells or IFN-␥ (11).…”

mentioning

confidence: 99%