**Pathogenesis of Inflammatory Bowel Disease**

**1** 

*Brasil* 

**The Role of COX-2 Inhibitors** 

Sender J. Miszputen3 and Marcello Franco1

*Universidade Federal de São Paulo, Escola Paulista de Medicina* 

Ana Paula R. Paiotti1, RicardoArtigiani-Neto1, Daniel A.Ribeiro1,2,

Since the introduction of acetylsalicylic acid (aspirin) as the first nonsteroidal antiinflammatory drug (NSAID) in 1897, NSAIDs have been widely used in the management of pain and inflammation (Botting, 2010; Vane et al., 1990; Wallace, 1997). Today, they are classified as traditional nonsteroidal antiinflammatory drugs (tNSAIDs), characterized by differing degrees of antiinflammatory, analgesic and antipyretic activity. tNSAIDs are among the most widely used medicines in the world. Unfortunately, they are associated with dose-dependent gastrointestinal (GI) adverse events ranging from dyspepsia (10-20%) to symptomatic and complicated ulcers (1-4%) (Scheiman, 2006; Wolfe et al., 1999). The mechanism of tNSAIDs action is attributed to the cyclooxygenase (COX) inhibition (Botting, 2010; Vane, 1971). Cyclooxygenase is a key rate-limiting enzyme that exists in at least two isoforms: COX-1 is observed constitutively expressed in various tissues, whereas COX-2 does not appear to be expressed except at very low levels in most tissues and is rapidly upregulated in response to growth factors and cytokines. More recently, COX-2 has been implicated in several distinct cellular mechanisms, such as angiogenesis, proliferation and the prevention of apoptosis (Dempke et al., 2001). New antiinflammatory drugs have been synthesized, such as selective COX-2 inhibitors (anti-COX-2), however, these drugs may present side effects, such as the ability to modify the epithelial barrier. Inflammatory bowel disease (IBD) is a common chronic gastrointestinal disorder characterized by alternating periods of remission and active intestinal inflammation. The precise etiology of IBD, including Crohn´s disease (CD) and ulcerative colitis (UC), remains unclear. However, environmental factors, immunological disturbances, genetic influences and the presence of certain chemical mediators (cytokines) have been established as putative participants in the pathogenesis of the disease (Barbieri, 2000; Lashner, 1995;

In the last few decades, the development of experimental models for studying IBD has greatly contributed to enhance understanding of the immunological mechanisms involved, such as changes in the gut epithelial barrier (Colpaert et al, 2001; Shorter et al, 1972). IBD seems to occur when luminal antigens from the bacterial flora stimulate the immune system

**1. Introduction** 

Podolsky, 2002).

**on Experimental Colitis** 

*1Departament of Pathology 2Departament of Biosciences 3Division of Gastroenterology* 
