This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Despite decades of research, the basic pathogenic mechanisms involved in inflammatory bowel disease (IBD) are still unknown. Many therapies are currently available, but there are still no cures for Crohn?s disease and ulcerative colitis whose major symptoms include abdominal pain, ulceration, bleeding, weight loss, and diarrhea. Clinical observations have suggested that intestinal bacteria might trigger, and perhaps exacerbate, the inflammatory response. It is more likely, however, that the pathogenesis of IBD is not associated with any specific pathogen per se, but with bacterial products, some of which have been detected in the gut of patients. The central hypothesis of this proposal is that bacterial peptides such as N-formyl-methionyl-leucyl-phenylalanine (fMLP) may influence the inflammatory response in the relapse phase of chronic colitis through an increase in gene expression of pro- inflammatory cytokines, and through a decrease in tissue viability and alteration of motility. FMLP has been found in the intestine of patients, and there is evidence that epithelial transporters for this molecule are abnormally expressed in inflammation. Recent discoveries suggest that a dysregulated immune response is directed against the normal bacterial flora in IBD, but little is known about the complex interactions occurring between pro- and anti-inflammatory cytokines. The central hypothesis will be systematically tested as follows: 1. The role of fMLP in a chronic ?reactivated? model of colitis and its ability to cause reactivation by itself will be investigated (Hypothesis: fMLP can initiate the relapse of inflammation in this model and contribute to the pathogenesis of colitis in the relapse phase.). 2. The levels of various cytokines after administration of fMLP in chronic ?reactivated? colitis will be measured (Hypothesis: If damage is increased by fMLP, then an increase in pro-inflammatory cytokines, or a change in the balance of the immune system, will be observed.). 3. The role of fMLP in the secretory responses and motility changes of the intestine in chronic ?reactivated? colitis will be evaluated (Hypothesis: Alterations of cytokine levels and release of neuromodulators by administration of fMLP in a reactivated model of animal colitis may alter the ion transport processes and contractile responses of the colon, thus contributing to the diarrhea observed in the human condition.). Knowledge of the immunoregulatory pathways evoked in response to bacterial peptides in chronic colitis will provide new avenues for potential therapeutic intervention in the future, and will solve the controversy over the effectiveness of antibiotic treatment.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Research Centers in Minority Institutions Award (G12)
Project #
5G12RR003050-26
Application #
8357063
Study Section
Special Emphasis Panel (ZRR1-RI-1 (01))
Project Start
2011-01-01
Project End
2011-12-31
Budget Start
2011-01-01
Budget End
2011-12-31
Support Year
26
Fiscal Year
2011
Total Cost
$123,297
Indirect Cost
Name
Ponce School of Medicine
Department
Type
DUNS #
105742043
City
Ponce
State
PR
Country
United States
Zip Code
00732
Jimenez-Torres, Gladys J; Wojna, Valerie; Rosario, Ernesto et al. (2017) Assessing health-related resiliency in HIV+ Latin women: Preliminary psychometric findings. PLoS One 12:e0181253
Abreu-Delgado, Yamilka; Isidro, Raymond A; Torres, Esther A et al. (2016) Serum vitamin D and colonic vitamin D receptor in inflammatory bowel disease. World J Gastroenterol 22:3581-91
de Jesus, Edelmarie Rivera; Isidro, Raymond A; Cruz, Myrella L et al. (2016) Adoptive Transfer of Dendritic Cells Expressing Fas Ligand Modulates Intestinal Inflammation in a Model of Inflammatory Bowel Disease. J Clin Cell Immunol 7:
Couvertier-Lebron, Carmen E; Dove, Rachel; Acevedo, Summer F (2016) What You Do Not Know Could Hurt You: What Women Wish Their Doctors Had Told Them About Chemotherapy Side Effects on Memory and Response to Alcohol. Breast Cancer (Auckl) 10:229-238
López, Pablo; Rivera-Amill, Vanessa; Paulino-Ramirez, Robert et al. (2015) Short Communication: HIV-1 Subtype B in the Dominican Republic: Evolution and Molecular Epidemiology. AIDS Res Hum Retroviruses 31:679-84
Isidro, Raymond A; Isidro, Angel A; Cruz, Myrella L et al. (2015) Double immunofluorescent staining of rat macrophages in formalin-fixed paraffin-embedded tissue using two monoclonal mouse antibodies. Histochem Cell Biol 144:613-21
Sosa-García, Bernadette; Vázquez-Rivera, Viviana; González-Flores, Jonathan N et al. (2015) The Retinoblastoma Tumor Suppressor Transcriptionally Represses Pak1 in Osteoblasts. PLoS One 10:e0142406
Perez-Torres, Emily M; Ramos-Ortolaza, Dinah L; Morales, Roberto et al. (2015) Morphine administration during low ovarian hormone stage results in transient over expression of fear memories in females. Front Behav Neurosci 9:129
Isidro, Raymond A; Cruz, Myrella L; Isidro, Angel A et al. (2015) Immunohistochemical expression of SP-NK-1R-EGFR pathway and VDR in colonic inflammation and neoplasia. World J Gastroenterol 21:1749-58
Norman, Lisa R; Basso, Michael (2015) An Update of the Review of Neuropsychological Consequences of HIV and Substance Abuse: A Literature Review and Implications for Treatment and Future Research. Curr Drug Abuse Rev 8:50-71

Showing the most recent 10 out of 170 publications