08-4
Chapter One
Molecular Mechanisms
of Glucocorticoid Receptor Action
Pankaj Bhavsar and Ian M. Adcock
1.1 Introduction
Glucocorticoids are the most effective therapy for the treatment of many chronic
inflammatory diseases such as asthma and inflammatory bowel disease (Ito et al.,
2006a). In contrast to the situation in asthma, chronic obstructive pulmonary disease
(COPD), a common and debilitating chronic inflammatory disease of the lung, is
glucocorticoid insensitive (Barnes, 2000a, b; Culpitt et al., 2003).
Glucocorticoids act by binding to cytosolic glucocorticoid receptors (GRs), which
upon binding become activated and rapidly translocate to the nucleus. Within the
nucleus, GR either induces transcription of genes such as secretary leukocyte proteinase
inhibitor (SLPI)(Abbinante-Nissen et al., 1995) and mitogen-activated kinase
phosphatase-1 (Lasaetal., 2002) by binding to specific DNA elements (glucocorticoid
response element, GRE) at the promoter/enhancer of responsive genes, or reduces
inflammatory gene transcription induced by nuclear factor-kappa B (NF-[kappa]B) or other
pro-inflamm ... read full excerpt from Overcoming Steroid Insensitivity in Respiratory Disease ebook
