Intestinal immunomodulation. Role of regulative peptides and promising pharmacological activities.
About 50 peptides, and a similar number of peptide receptors, are known to be present in the gut and this amount is likely to rise significantly over the next few years. While there has been a massive research effort to define their functions and their anatomical distribution in the central nervous system (CNS), the understanding of their roles in the gut is far more limited. Classically, the physiological functions include the control of motility, fluids, electrolytes, and digestive enzymes secretion, or vascular and visceral pain function, and more recently, the role-played in cell proliferation and survival, and in immune-inflammatory responses. The term inflammatory bowel disease (IBD) that encompasses Crohn's disease and ulcerative colitis, is clearly an inflammatory disease where several mediators such as cytokines, chemokines, prostanoids, nitric oxide or free radicals, produced by infiltrating cells, play a critical role in intestine tissue alteration. Some peptides, initially known for their neuroregulative properties, have been suggested to act as endogenous immune factors, with predominant antiinflammatory effects. Based on these actions, these molecules are proposed as potential agents for the treatment of IBD and selective peptide analogs are being developed as novel therapeutic strategies for IBD patients. Patients with IBD have an increased risk for developing colorectal cancer (CRC). Up to the present time, no known genetic basis has been identified to explain CRC predisposition in these IBD. Instead, it is assumed that chronic inflammation is what causes cancer. This is supported by the fact that colon cancer risk increases with longer duration of colitis, greater anatomic extent of colitis, the concomitant presence of other inflammatory manifestations, and the fact that certain drugs used to treat inflammation, may prevent the development of CRC. However, though different regulative peptides play a beneficial role in experimental IBD, an increasing number of articles about cancer pathology are starting to implicate different peptides in tumor initiation and progression. The complexities of cancer could be described in terms of a small number of underlying principles and the malignant growth is dependent upon a multi-step process including different basic essential alterations. The activities of many peptides that are overexpressed in cancer cells help them to develop several of the molecular and physiological features that are now considered the basis of malignant growth. These collective findings implicate regulative peptides, receptors, or peptide-levels modulators, as important biological targets for developing intervention strategies against intestinal immunological disorders and cancers.
Motilva
V
V
Department of Pharmacology, Faculty of Pharmacy, University of Seville, Spain. motilva@us.es
Talero
E
E
Calvo
J R
JR
Villegas
I
I
Alarcón-de-la-Lastra
C
C
Sánchez-Fidalgo
S
S
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000209:etiology / Q000276:immunology; D016503:Drug Delivery Systems; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D015212:Inflammatory Bowel Diseases / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D007422:Intestines / Q000276:immunology; D010455:Peptides / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D010455:Peptides