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.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Research Centers in Minority Institutions Award (G12)
Project #
Application #
Study Section
Special Emphasis Panel (ZRR1-RI-1 (01))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Ponce School of Medicine
United States
Zip Code
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:
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
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
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
Quiñones, Maria; Urrutia, Rebecca; Torres-Reverón, Annelyn et al. (2015) Anxiety, coping skills and hypothalamus-pituitary-adrenal (HPA) axis in patients with endometriosis. J Reprod Biol Health 3:
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
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
Colón-Caraballo, Mariano; Monteiro, Janice B; Flores, Idhaliz (2015) H3K27me3 is an Epigenetic Mark of Relevance in Endometriosis. Reprod Sci 22:1134-42
Rivera-Rivera, Yainyrette; García, Yashira; Toro, Valerie et al. (2014) Depression Correlates with Increased Plasma Levels of Inflammatory Cytokines and a Dysregulated Oxidant/Antioxidant Balance in HIV-1-Infected Subjects Undergoing Antiretroviral Therapy. J Clin Cell Immunol 5:

Showing the most recent 10 out of 163 publications