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PPAR ? an important regulator of monocyte/macrophage function

100%

von K. A., Brune B.

Archivum Immunologiae et Therapiae Experimentalis

2003

vol. 51

issue 4

219-226

Regulation of monocyte/macrophage function is important to coordinate immune responses. Their contact with invading pathogens activates signaling pathways that provoke pro-inflammatory gene expression and thus causing a locally restricted inflammation. Recently, the peroxisome proliferator activated receptor (PPAR) has been identified to antagonize pro-inflammatory responses in monocytes/macrophages causing an anti-inflammatory and/or desensitized phenotype to predominate. For PPAR general mechanisms in facilitating the transition from a pro- to an anti-inflammatory phenotype have been elucidated. PPAR is a member of the nuclear receptor superfamily and activated upon endogenous as well as exogenous agonist binding. Here we focus on its role in monocyte/macrophage biology in affecting inflammation. Summarizing current information, a model is proposed, giving rise to potential new therapeutic possibilities for the treatment of diseases presumably involving PPAR-dependent regulatory circuits.

Peroxisome proliferator-activated receptor gamma (PPARgamma) and sepsis

81%

von_ K. A., Soller M., Brune B.

2007

vol. 55

issue 1

19-25

This review describes the role of the nuclear hormone receptor PPARgamma as a double-edged sword in sepsis. On the one hand, PPARgamma inhibits pro-inflammatory gene expression, predominantly by scavenging transcription factors and their cofactors, thus preventing them from binding to their cognate binding sites in the promoters of target genes. The expressions of the affected genes, such as those for inducible nitric oxide synthase, TNF-alpha, or IL-1beta are repressed. Therefore, PPARgamma is suggested to be beneficial in hyper-inflammatory diseases, such as sepsis. In n animal models of sepsis, PPARgamma agonist pretreatment auspiciously attenuated inflammation compared with control animals, accompanied by their improved survival rate. On the other hand, PPARgamma provokes apoptosis, which in the hyper-inflammatory phase of sepsis might be helpful because the number of immune cells, such as monocytes, macrophages, and neutrophils, involved in secreting high amounts of pro-inflammatory mediators will be reduced. In contrast, during the anti-inflammatory phase, cell death of immune cells, especially of T lymphocytes, is supposed to be deleterious. Under these circumstances, a second infection cannot be adequately answered, thus causing septic shock and multi-organ dysfunction syndrome. Therefore the role of PPARgamma is still ambiguous. Particularly its role in initiating apoptosis awaits further clarification to finally elucidate its impact on sepsis development.

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2 Archivum Immunologiae et Therapiae Experimentalis

1 2007

1 2003

2 Brune B.

1 Soller M.

1 von K. A.

1 von_ K. A.

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PPAR ? an important regulator of monocyte/macrophage function

Peroxisome proliferator-activated receptor gamma (PPARgamma) and sepsis