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Induction of High Mobility Group-I(Y) Protein by Endotoxin and Interleukin-1β in Vascular Smooth Muscle Cells

1999; Elsevier BV; Volume: 274; Issue: 3 Linguagem: Inglês

10.1074/jbc.274.3.1525

1083-351X

Andrea Pellacani, Michael T. Chin, Philippe Wiesel, Maureen Ibanez, Anand Patel, Shaw‐Fang Yet, Chung-Ming Hsieh, Joseph Paulauskis, Raymond Reeves, Mu-En Lee, Mark A. Perrella,

Inflammatory mediators and NSAID effects

Nonhistone chromosomal proteins of the high mobility group (HMG) affect the transcriptional regulation of certain mammalian genes. For example, HMG-I(Y) controls cytokine-mediated promoters that require transcription factors, such as nuclear factor-κB, for maximal expression. Even though a great deal is known about how HMG-I(Y) facilitates expression of other genes, less is known about the regulation of HMG-I(Y) itself, especially in cells in primary culture. Therefore we investigated the effect of endotoxin and the cytokine interleukin-1β on HMG-I(Y) expression in vascular smooth muscle cells. Induction of HMG-I(Y) peaked after 48 h of interleukin-1β stimulation (6.2-fold) in cells in primary culture, and this increase in mRNA corresponded to an increase in HMG-I(Y) protein. Moreover, immunohistochemical staining revealed a dramatic increase in HMG-I(Y) protein expression in vascular smooth muscle cells after endotoxin stimulation in vivo . This increase in HMG-I(Y) expression (both in vitro and in vivo ) mirrored an up-regulation of inducible nitric oxide synthase, a cytokine-responsive gene. The functional significance of this coinduction is underscored by our finding that HMG-I(Y) potentiated the response of inducible nitric oxide synthase to nuclear factor-κB transactivation. Taken together, these studies suggest that induction of HMG-I(Y), and subsequent transactivation of iNOS, may contribute to a reduction in vascular tone during endotoxemia and other systemic inflammatory processes.