Inflammation expression profiling

Figure 15-4 In silico subtraction method for mechanistic study to compare the hepatic gene expression profile induced by compound X to other compounds that induce hepatic APR secondary to inflammation at sites other than the liver. In the proposed simple model, compound X-induced gene expression change has two components. One is vasculitis specific the other is acute phase response (APR) specific. By subtracting the APR specific component, we might select candidate genes that are specifically associated with the hepatic vascular lesion Diclofenac known to induce APR without triggering vasculitis in liver is used to subtract genes activated by hepatic APR from the compound X response.

N.G. Sandler, M.M. Mentink-Kane, A.W. Cheever, T.A. Wynn, Global gene expression profiles during acute pathogen-induced pulmonary inflammation reveal divergent roles for Thl and Th2 responses in tissue repair,/. Immunol. 2003, 171, 3655-3667. 

Heart failure, ischemia, and vascular inflammation have specific associated miRNAs (Table 37.5). A pathological condition caused by an injury may reflect several conditions thus, the miRNA expression profile may not be unique. 

Insulin resistance occurs when the normal response to a given amount of insulin is reduced. Resistance of liver to the effects of insulin results in inadequate suppression of hepatic glucose production insulin resistance of skeletal muscle reduces the amount of glucose taken out of the circulation into skeletal muscle for storage and insulin resistance of adipose tissue results in impaired suppression of lipolysis and increased levels of free fatty acids. Therefore, insulin resistance is associated with a cluster of metabolic abnormalities including elevated blood glucose levels, abnormal blood lipid profile (dyslipidemia), hypertension, and increased expression of inflammatory markers (inflammation). Insulin resistance and this cluster of metabolic abnormalities is strongly associated with obesity, predominantly abdominal (visceral) obesity, and physical inactivity and increased risk for type 2 diabetes, cardiovascular and renal disease, as well as some forms of cancer. In addition to obesity, other situations in which insulin resistance occurs includes... 

Since adhesion molecules are of pivotal importance in cell trafficking and thus inflammation, they could constitute good therapeutic targets in RA. In fact, a murine mAb to intercellular adhesion molecule (ICAM)-l proved to lead to clinical improvement, (140) but repeated administration may have less effects, and the side-effect profile was also of major concern (141). Thus, anti-ICAM-1 may not be the strategy of choice. In this context it should be mentioned that TNFa blockade leads not only to clinical benefit but also to reduction of adhesion molecule expression. 

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