Pancreatic stellate cells: new target in the treatment of chronic pancreatitis.
Chronic pancreatitis (CP) is characterized by progressive fibrosis, pain and/or loss of exocrine and endocrine functions. Recent in vitro and in vivo experiments have proven objectively the role of activated pancreatic stellate cells (PSC) in fibrogenesis in CP. Molecular mediators shown to regulate the pathogenesis include transforming growth factor beta (TGF-beta), platelet-derived growth factor (PDGF), and pro-inflammatory cytokines such as IL-1, IL-6 and TNF-alpha. Furthermore, molecular pathways involving mitogen-activated protein kinases (MAPK), phosphatidyl inositol 3-kinase (PI3K), Ras superfamily G proteins, serine threonine protein kinase Raf-1 and peroxisome proliferator activated receptor gamma (PPAR-gamma) have been elucidated. Understanding of the pathogenesis has led to identification of novel molecular targets and development of potential newer therapeutic agents. Those found to retard the progression of experimental CP and fibrosis in animal models include interferon (IFN) beta and IFN-gamma; a Japanese herbal medicine called Saiko-keishi-to (TJ-10); curcumin; PPAR-gamma ligand (troglitazone); antioxidants (vitamin A, vitamin E, DA 9601 and epigallocatechin-3-gallate); a protease inhibitor (camostat mesilate) and hydroxymethylglutaryl-CoA inhibitor (lovastatin). This review summarizes the current literature addressing the role of different pharmacological agents aimed at reducing or preventing inflammation and the consequent fibrogenesis in CP.
Talukdar
Rupjyoti
R
Department of Gastroenterology, Pushpawati Singhania Research Institute, New Delhi, India.
Tandon
Rakesh K
RK
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002477:Cells / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D010179:Pancreas / Q000473:pathology*; D050500:Pancreatitis, Chronic / Q000188:drug therapy* / Q000473:pathology*; D051381:Rats
D000893:Anti-Inflammatory Agents