François M, Richette P, Corvol M-T
Institut National de la Santé et de la Recherche Médicale, Université Paris, Paris, France.
Drug News Perspect. 2005 May;18(4):257-61. doi: 10.1358/dnp.2005.18.4.908660.
Antiinflammatory effects by peroxisome proliferator-activated receptor gamma (PPARgamma) agonists have been previously reported. However, PPARgamma dependency and the molecular mechanism involved in these effects require more investigation to clearly demonstrate whether PPARgamma is a key modulator of the antiinflammatory process. This would permit the design of more specific agonists or antagonists able to address the gamma subtype without cross reactions with other transcription factors, thus preventing undesirable side effects. However, several hurdles need to be taken into consideration, such as the coexpression of several PPAR isotypes in the same cell type. As PPARgamma and -alpha seem to play equal antiinflammatory roles, determining the subset of specific PPAR subtype target genes appears to be crucial. The work described here is our current understanding of the modulations of interleukin-1 target gene expression by PPARgamma and its ligands.
过氧化物酶体增殖物激活受体γ（PPARγ）激动剂的抗炎作用此前已有报道。然而，PPARγ的依赖性以及这些作用所涉及的分子机制需要更多研究，以明确证明PPARγ是否为抗炎过程的关键调节因子。这将有助于设计更具特异性的激动剂或拮抗剂，能够作用于γ亚型而不与其他转录因子发生交叉反应，从而避免不良副作用。然而，需要考虑几个障碍，例如同一细胞类型中几种PPAR亚型的共表达。由于PPARγ和-α似乎发挥同等的抗炎作用，确定特定PPAR亚型靶基因的子集似乎至关重要。本文所述的工作是我们目前对PPARγ及其配体对白细胞介素-1靶基因表达调节的理解。
