Inflammation

, Volume 28, Issue 1, pp 23–31 | Cite as

Signaling Pathways for Fcγ Receptor-Stimulated Tumor Necrosis Factor-α Secretion and Respiratory Burst in RAW 264.7 Macrophages

Abstract

Fcγ receptor (FcγR) signaling mediates several important macrophage functions including cytokine secretion and respiratory burst. The present study describes the development of a model using the macrophage cell line, RAW 264.7 for studying FcγR-stimulated tumor necrosis factor-α (TNF-α) secretion and hydrogen peroxide (H2O2) production. In unprimed cells these functions were low but pretreatment with interferon-γ augmented FcγR-stimulated TNF-α secretion and H2O2 production to levels that were about half that caused by lipopolysaccharide (LPS) and zymosan, respectively. Studies on the signaling pathways found that TNF-α secretion stimulated by either FcγR or LPS was decreased by inhibitors of PKC, MAPK p42/p44, and MAPK p38. TNF-α secretion was also reduced by the combination of PLC and PLD inhibitors but not by the individual inhibitors alone. H2O2 production stimulated by either FcγR or zymosan was blocked by inhibitors of PKC, PLC, PLD, and MAPK p42/44 but not by MAPK p38. Thus, interferon-γ treated RAW 264.7 cells are a model of inflammatory macrophages and are well suited for further study of these signaling pathways.

tumor necrosis factor-alpha respiratory burst Fc gamma receptors protein kinase C mitogen activated protein kinase 

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Copyright information

© Plenum Publishing Corporation 2004

Authors and Affiliations

  1. 1.Center for Cardiovascular SciencesAlbany Medical CollegeAlbany
  2. 2.Center for Cell Biology and Cancer ResearchAlbany Medical CollegeAlbany

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